Tools

Five gnomAD tools, plus three for SQL analytics over the DuckDB-backed canvas tables the list tools materialize:

gnomad_get_variant

The "how common, is it benign" answer in one call.

• Batch up to 25 IDs per call, each a chrom-pos-ref-alt variantId (e.g. 1-55051215-G-GA) or an rsID (e.g. rs11591147)
• Per-item partial success — a malformed or absent ID lands in failed[] without failing the others
• Per-ancestry frequency vector is returned in full, never collapsed to a single global AF
• Reports which callset(s) (exome / genome) carry the variant, quality flags, transcript consequence, in-silico predictor scores, and the ClinVar significance gnomAD joins per variant
• An empty found[] for a well-formed ID means the variant is not in the chosen dataset — pair with gnomad_get_coverage to confirm the position is callable before concluding true absence

gnomad_get_gene_constraint

The orthogonal axis to allele frequency — a loss-of-function variant matters far more in a gene intolerant to being broken.

• Accepts an HGNC symbol (PCSK9) or an Ensembl gene ID (ENSG00000169174)
• Returns pLI (>0.9 intolerant), LOEUF / oe_lof_upper (<0.6 intolerant in v4, <0.35 in v2) with its lower bound, observed/expected ratios for LoF / missense / synonymous, and the three Z-scores
• Many genes have null constraint (sparse upstream) — null fields are reported as such, never fabricated
• constraint_flags surfaces v4 beta caveats flagged by the gnomAD team

gnomad_list_gene_variants

List variants across a gene, transcript, or region, then SQL the full set.

• Supply exactly one of gene, transcript_id, or region (chrom-start-stop, 1-based inclusive)
• Optional filters: one consequence_class (lof / missense / synonymous / other) and/or a maximum allele frequency
• The full result is staged on a DataCanvas table named gene_variants with an inline preview returned alongside canvas_id and table_name — query it with gnomad_dataframe_query to rank by AF, count by consequence, or group across the complete set
• Reusing a canvas_id REPLACES the staged table; it does not append
• When the canvas is disabled (CANVAS_PROVIDER_TYPE != duckdb) the tool returns a capped inline preview with spilled=false and the SQL path is unavailable

gnomad_get_coverage

Disambiguate a true absent variant from an uncallable position.

• Supply exactly one of gene, transcript_id, or region
• Returns mean and median read depth plus the mean fraction of samples covered at each threshold (1× through 100×), summarized per callset track
• coverage_source narrows to one track (exome / genome); omit to return every available track
• A variant missing from a well-covered region is informative; one missing from a poorly-covered region is not

gnomad_search_clinvar

Gene-panel curation depth beyond the per-variant ClinVar join, via NCBI E-utilities.

• Returns a gene's classified ClinVar variants — clinical significance, review status with a 0–4 star rating, associated conditions, molecular consequences, and submission counts
• Optional filters: clinical_significance (e.g. pathogenic) and a minimum star rating (min_review_stars, 0–4)
• The full set is staged on the clinvar_variants canvas table with an inline preview; reusing a canvas_id REPLACES that table
• Keyless, but honors NCBI_API_KEY for a higher rate limit (10 vs 3 req/s)

Canvas dataframe tools

gnomad_dataframe_query, gnomad_dataframe_describe, and gnomad_dataframe_drop operate on the canvas tables the list tools stage.

• gnomad_dataframe_query runs single-statement SELECTs only — writes, DDL, and file/HTTP table functions are rejected by the canvas gate
• gnomad_dataframe_describe returns each staged table's name, row count, and column schema — call it before writing SQL
• gnomad_dataframe_drop is a deliberate mutation (readOnlyHint: false); it stays absent from tools/list unless GNOMAD_DATAFRAME_DROP_ENABLED=true
• All three require CANVAS_PROVIDER_TYPE=duckdb; without it they return a canvas_disabled error

Resources and prompts

All resource data is also reachable via tools. The list tools (gnomad_list_gene_variants, gnomad_get_coverage, gnomad_search_clinvar) return analytical row sets rather than stable single-URI documents, so they are not exposed as resources — call the tools instead.

Features

Built on @cyanheads/mcp-ts-core:

• Declarative tool, resource, and prompt definitions — single file per primitive, framework handles registration and validation
• Unified error handling — handlers throw, framework catches, classifies, and formats
• Typed error contracts with agent-facing recovery hints
• Pluggable auth: none, jwt, oauth
• Structured logging with optional OpenTelemetry tracing
• STDIO and Streamable HTTP transports

gnomAD-specific: