Rare Disease Diagnosis (ToolUniverse Claude Skill)

A ToolUniverse agent skill that builds a rare-disease differential diagnosis from a patient’s phenotype and genetic data by matching HPO terms to candidate diseases, prioritizing genes, and interpreting variants under ACMG criteria.

   
Type Claude Skill (one of ToolUniverse’s pre-built agent skills)
Supplier Zitnik Lab, Harvard Medical School
Availability GA — part of the ToolUniverse skills collection (skills/tooluniverse-rare-disease-diagnosis/)
Pricing Free / OSS (Apache-2.0); reasoning runs locally, database calls go through the ToolUniverse MCP server
Capabilities Read-only — drives ToolUniverse tool calls; no data writes
Verified works · 2026-07-20
Security cleared · 2026-07-20 — provenance matches Zitnik Lab, Apache-2.0, skill dir confirmed, no OSV advisories

How to install

This skill calls ToolUniverse tools, so the ToolUniverse MCP server must be installed first (see the ToolUniverse page). Simplest registration:

claude mcp add --transport stdio tooluniverse -- uvx tooluniverse

Then add the skills:

  • Claude Code — install the whole skill collection (the skill resolves as tooluniverse-rare-disease-diagnosis): 
    npx skills add mims-harvard/ToolUniverse
  • Manual / other agents — copy just this skill directory into your skills folder: 
    git clone https://github.com/mims-harvard/ToolUniverse
cp -r ToolUniverse/skills/tooluniverse-rare-disease-diagnosis ~/.claude/skills/

The skill sets disable-model-invocation: true upstream, so invoke it explicitly (e.g. ask Claude to “use the rare-disease-diagnosis skill”) rather than relying on automatic dispatch.

What it does

Runs a phenotype-driven differential-diagnosis workflow, grading evidence by tier and writing a progressively-updated report:

  • Clinical reasoning — forms an initial 3–5 candidate differential from the presentation.
  • Phenotype matching — HPO_search_terms maps symptoms to Human Phenotype Ontology terms.
  • Candidate diseases — Orphanet_search_diseases, Orphanet_get_genes, OMIM_search, DisGeNET_search_gene identify candidate diseases and associated genes.
  • Gene prioritization — MARRVEL_get_gene, MARRVEL_get_omim_phenotypes, ClinGen validation, GTEx_get_expression_summary, plus CELLxGENE/ChIP-Atlas and KEGG/IntAct pathway context.
  • Variant interpretation — FAVOR_annotate_variant, ClinVar_get_variant_details, gnomad_get_variant, with EVE and SpliceAI for missense/splice effects; AlphaFold2 + InterPro for structure-based analysis.
  • Literature & synthesis — PubMed, bioRxiv/medRxiv, and OpenAlex evidence, synthesized into a tiered (T1–T4) diagnostic report.

Primary use cases: undiagnosed-disease-program support, phenotype-to-gene-panel prioritization, ACMG variant classification, differential-diagnosis review.

Notes

It is a reasoning layer over ToolUniverse; without the MCP server registered, the tool calls fail. The skill operates on user-supplied phenotype and variant data rather than raw sequencing files, and OMIM access may require a user account/license for full content. Outputs are decision-support reasoning, not a clinical diagnosis. ToolUniverse ships ~68 such skills; the research, repurposing, precision-oncology, pharmacovigilance, and drug-drug-interaction workflows are catalogued separately.

Sources

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