BRaVa

An MCP server for the Biobank Rare Variant Analysis (BRaVa) consortium's association results: rare coding-variant, gene-based tests meta-analysed across ~1.2M individuals from 10 global biobanks, 44 harmonised traits, 7 ancestry strata.

Summary statistics only. Not for clinical use.

SQL over the whole table

query runs read-only SQL against all 61,791,444 gene-level rows: every gene x trait x variant-mask x MAF-cutoff x ancestry cell, with the Burden, SKAT and SKAT-O p-values, the effect size and its standard error, and the cross-cohort heterogeneity test. The database is local, so a query costs no network.

-- what does this gene do
SELECT trait, mask, p_skato, beta FROM results
WHERE gene='PCSK9' AND ancestry='All' AND mask<>'synonymous'
ORDER BY p_skato LIMIT 20

-- most pleiotropic genes
SELECT gene, count(DISTINCT trait) traits FROM results
WHERE ancestry='All' AND p_skato < 1.39e-7 GROUP BY gene ORDER BY traits DESC

-- what a European-only study would have missed
SELECT a.gene, a.trait, a.p_skato FROM results a
WHERE a.ancestry='AFR' AND a.p_skato < 2.5e-6 AND NOT EXISTS (
  SELECT 1 FROM results e WHERE e.ancestry='EUR'
  AND e.gene_idx=a.gene_idx AND e.pheno=a.pheno AND e.p_skato < 2.5e-6)

Tools

Tool	What it is for
query	Read-only SQL over the whole gene-level table
schema	Tables, columns, runnable recipes, and the traps that make a valid query scientifically wrong. Read this first
gene_phenotype_detail	Cross-ancestry replication for a gene-trait pair, or a screen over a hit list
variants	Single-variant results, genome-wide for a trait or inside one gene

Why the other three exist.

gene_phenotype_detail computes the concordance count over the five superpopulations only, excluding All and non_EUR, which pool the same individuals. A query that aggregates over every ancestry double-counts.

variants fetches over HTTP. The variant-level release is a separate upstream format of 3.09 GiB across ~176,000 objects, against 1.19 GiB for the gene-level data, and it is not included in the local database.

schema() returns the tables and columns, runnable query templates, and ten pitfalls: effect sizes belong to a different test than the p-value beside them, one mask is a calibration control rather than a biological category, ancestry strata overlap, a p-value of exactly zero is the strongest result rather than a missing one, and six more. Read it before writing SQL.

The database

873 MB, published as a release asset and downloaded once into ~/.cache/brava-mcp/ at first use. Cloning this repo costs 3.9 MB.

Built by etl/build_db.py from the 280 published phenotype/{P}.{ANC}.json files. Those carry the same data as the 19,541 per-gene files, so the pivot is chosen for politeness: 280 requests against 19,541 for identical coverage, once, rather than one per gene consulted forever. Class B operations are the scarce resource on the upstream free tier; egress is free on R2.

Sorted on the low-cardinality key columns and built without ART indexes: 2.49 GB with indexes, 1.75 GB without, 0.87 GB sorted. No index is missed, because these are filtered scans and DuckDB's zonemaps already serve them. Every query above returns in under 70 ms.

Running it

make sync                 # install
make db                   # download the published database (873 MB, once)
make test                 # offline suite
make test-all             # + live-data checks
make eval                 # 14 benchmark questions, answers derived independently
make serve                # HTTP daemon on :3163
uv run python server.py   # stdio

Rebuild the database from upstream with uv run python etl/build_db.py (~200 s: 120 s of downloads, 76 s of loading, then the sorted compaction).

Variable	Default	Purpose
MCP_TRANSPORT	stdio	http for the shared daemon
MCP_PORT	3163	daemon port
BRAVA_DB_URL	the release asset	where to fetch the database
BRAVA_DB_PATH	~/.cache/brava-mcp/brava.duckdb	local database
BRAVA_VARIANT_BASE_URL	upstream R2	variant-level files

Reading the results

• beta > 0 increases risk (binary traits) or the trait value (quantitative). beta and se always come from the inverse-variance-weighted Burden meta-analysis, including on rows where you read p_skato. There is no SKAT-O effect size.
• SKAT-O is the primary omnibus test. Burden is most powerful when a gene's variants point the same way; SKAT when they are mixed.
• The synonymous mask is a calibration control. A significant synonymous result indicates residual test inflation, not biology.
• Thresholds from the flagship paper: gene × mask Bonferroni 1.39e-7, gene-level Cauchy 2.5e-6, variant-level 1.82e-8.
• BRaVa carries no allele frequencies and no common-variant GWAS. Variant rows link to gnomAD for the former.

schema() returns all of this, plus five more traps, alongside the columns.

Evaluation

evals/questions.json holds fourteen questions, all fourteen resolved directly from the raw upstream files by evals/resolve_golds.py, which imports nothing from brava, so the benchmark cannot agree with a decoding bug and doubles as an upstream-drift detector.

evals/selfcheck.py walks each question through the tools: currently 14/14, a median of one call per question, and zero outbound HTTP requests for the whole set. It checks each question's evidence (the values the tools must return) and never its answer, because several answers are conclusions no string match can verify. So it proves the data is reachable and at what cost, not that a model reaches the right conclusion; that half needs a model-in-the-loop runner and is still missing.

Traffic

Gene-level questions are local, so they cost the upstream project nothing at all. Only variants fetches, and each file is cached permanently. Building the database costs 280 requests, once. See nikbaya/brava_browser#1 for the conversation with the upstream author.

Citation

Palmer, Hill, Hodgson, et al. Rare variant association analyses across 10 global biobanks. medRxiv (2026). doi:10.64898/2026.05.21.26353759

The database is derived from that release via the BRaVa browser's published files, and is redistributed under the browser's MIT licence.

Licence

MIT.