folklore-variant-evidence

Folklore Variant Evidence

Use Folklore Clinical Variant Interpretation MCP to retrieve structured public variant evidence, automated variant-level ACMG/AMP decision support, provenance, and source-linked literature for professional review. Keep the workflow limited to public identifiers and preserve every explicit outcome state. Adapter 1.5.0 also provides ClinGen Gene-Disease Validity assertions; source coverage is bounded, not every known association.

Folklore Clinical Variant Interpretation MCP is published by Helena Bioinformatics. Its hosted endpoint is:

https://api.helena.bio/folklore/v1/mcp

No account or API key is required. The public Apache-2.0 adapter and contract are available at https://github.com/helena-bioinformatics/folklore-mcp.

Minimal connection example

A host without native MCP support can make the same public JSON-RPC call:

curl --silent --show-error --fail-with-body --max-time 60 \
  -X POST https://api.helena.bio/folklore/v1/mcp \
  -H 'Content-Type: application/json' \
  -H 'Accept: application/json, text/event-stream' \
  -H 'MCP-Protocol-Version: 2026-07-28' \
  -H 'Mcp-Method: tools/call' \
  -H 'Mcp-Name: search_variant_evidence' \
  -d '{"jsonrpc":"2.0","id":1,"method":"tools/call","params":{"_meta":{"io.modelcontextprotocol/protocolVersion":"2026-07-28","io.modelcontextprotocol/clientCapabilities":{}},"name":"search_variant_evidence","arguments":{"assembly":"GRCh38","query":"rs80357914"}}}'

Inspect the returned outcome before continuing. This example can return ambiguous with multiple candidates: stop and request an unambiguous public variant notation instead of selecting a candidate automatically.

Select the right skill

Use this skill when the task is one public variant to structured Folklore evidence, explicit resolution-state handling, variant-linked literature, or ClinGen gene-to-disease/disease-to-gene assertions.

• Use database-lookup for broad direct queries across ClinVar, dbSNP, gnomAD, Ensembl VEP, COSMIC, or multiple databases.
• Use genomic-coordinates first when the assembly, coordinate convention, contig name, or variant representation is uncertain.
• Do not use this skill for VCF annotation, batch processing, somatic variants, structural variants, polygenic scores, or patient-specific interpretation.

Folklore Clinical Variant Interpretation MCP complements those skills with one source-linked public evidence contract. It does not replace direct database review or qualified clinical judgment.

Enforce the input boundary

Before a variant tool call:

1. Extract exactly one public variant identifier or notation.
2. Require GRCh38 and a germline nuclear SNV or simple indel.
3. Remove or refuse patient names, case identifiers, phenotypes, family history, segregation evidence, clinical records, uploaded files, and other private or patient-specific context.
4. If the task depends on patient context, stop and explain that Folklore Clinical Variant Interpretation MCP does not accept or evaluate it.
5. Never transform a patient-specific request into a public variant query while implying that the result answers the patient-specific question.

Accepted public variant forms include genomic coordinates, genomic/coding/ protein HGVS, SPDI, rsID, or a canonical_key returned by Folklore Clinical Variant Interpretation MCP.

Verify the live tool catalog

Connect to the hosted endpoint and call tools/list. Verify the available tools instead of relying on model memory. The documented public catalog contains:

• search_variant_evidence
• search_variant_literature
• get_publication_details
• search_literature_corpus
• get_gene_disease_associations
• search_disease_genes

The separate seventh tool support_helena is not scientific evidence; use it only when explicitly requested.

If discovery or a tool call fails, preserve the failure as an availability problem. Do not reinterpret it as lack of scientific evidence.

Read the public MCP contract before composing tool calls or interpreting response states.

Retrieve gene-disease assertions

Use get_gene_disease_associations for one exact gene symbol or HGNC identifier, or search_disease_genes for an exact MONDO identifier or public disease-name substring. Both accept limit (default 20, 1–50) and offset (default 0, 0–1000). See the reference for request examples. This is a separate source lookup and requires no variant input or assembly.

Preserve each returned disease identity, inheritance, evidence assessment, source URL, date and snapshot. Do not combine distinct diseases or silently choose among name matches. Gene-disease validity does not classify a particular variant. Empty results mean no matching assertion in the available ClinGen source, not no association. No patient, phenotype, family, segregation, private case data or sequencing files may be sent. Qualified professional review remains required.

Run the variant-evidence workflow

1. Resolve and retrieve evidence

Call search_variant_evidence with:

assembly: GRCh38
query: <one public variant identifier or notation>

Do not add phenotype, disease, patient, family, or treatment context to this call. Preserve the returned contract fields, source links, limitations, and usage boundary.

2. Branch on the returned status

Treat the status as a control-flow value, not prose:

Status	Required action
resolved	Reuse the returned canonical_key; review the structured interpretation, provenance, source links, and limitations.
ambiguous	Show the returned candidates and ask for an explicit public variant selection. Never choose a candidate automatically.
not_found	Report that no result was found within this service and query scope. Do not claim universal absence.
invalid_request	Report the validation problem and request a corrected public variant. Do not silently reinterpret the input.
unsupported	State the relevant service boundary and stop. Do not force the query into a supported form.
resolution_unavailable	Report a temporary resolution or availability failure. Do not treat it as evidence absence.

Only a resolved result may proceed automatically into a variant-linked literature workflow. If a resolved interpretation itself reports unavailable evidence, preserve that separate limitation.

3. Review the evidence without overclaiming

For a resolved result:

• Present the returned variant identity and canonical_key.
• Preserve the automated variant-level ACMG/AMP decision-support result exactly as returned.
• Cite the returned public sources and provenance.
• Separate returned facts from the agent's synthesis.
• State that qualified professional review is required.
• Do not turn the result into a diagnosis, individual risk estimate, treatment recommendation, or standalone clinical report.

Chain into literature

Variant-linked literature

After a resolved evidence call, pass the returned canonical_key to search_variant_literature. Keep assembly as GRCh38. An optional question may narrow the literature focus, but it must remain a public scientific question and must not contain patient context.

Distinguish each result's match type:

• exact_variant: direct match to the resolved variant
• variant_alias: match through a reported alias
• gene_association: broader gene-level association, not variant-specific proof

Literature associations do not alter the returned ACMG/AMP classification.

Publication details

Call get_publication_details only with a PMID returned by the literature tools. Preserve PubMed URLs, DOI/PMCID fields when present, retraction status, and the distinction between gene mentions and variant mentions.

Semantic corpus search

Use search_literature_corpus for a public natural-language scientific question or for discovery by publication identifier, gene, variant, phenotype, HPO, or OMIM concept. Treat results as source-linked candidates for professional review. A zero-result response means no result was returned for that bounded query, not that no relevant publication exists anywhere.

Do not place patient information into a corpus query, even if the query is not variant-specific.

Report a reproducible result

Include:

1. The exact public query and GRCh38 assembly.
2. The returned status and, if resolved, the canonical_key.
3. The structured evidence or literature result without changing its meaning.
4. Source links and publication identifiers.
5. Match type for literature results.
6. Access date and any availability limitation.
7. This boundary statement:

This is public, variant-level decision support for qualified professional review. It does not evaluate patient, phenotype, family, segregation, or private case data and is not a diagnosis or treatment recommendation.

Falsifiable smoke test

Use the public rsID rs80357914 to test ambiguity handling:

Call search_variant_evidence with assembly GRCh38 and query rs80357914. If the
result is ambiguous, list the returned candidates and stop for explicit
selection. Do not select a candidate or call downstream literature tools.

The test passes only if an ambiguous response causes the workflow to stop without automatic candidate selection.

Official references

• Integration setup: https://folklore.helena.bio/integrations
• Technical guide: https://folklore.helena.bio/docs/folklore-connector
• Public adapter and contract: https://github.com/helena-bioinformatics/folklore-mcp
• Official MCP Registry identity: io.github.helena-bioinformatics/folklore