BRaVa MCP
Enables querying rare-variant, gene-based association results across ~1.2M individuals from 10 global biobanks, supporting phenome-wide scans, replication screens across ancestries, and candidate list evaluation for 44 harmonized traits.
README
BRaVa MCP
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.
It ships the table, not a wrapper around it
The gene-level results are a single flat fact table, and a model already writes
SQL at expert level, so query hands it over: 61,791,444 rows, locally, no
network. Any question is a query, including the ones a fixed set of tools would
never have anticipated.
-- 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 |
The three non-query tools cover what SQL cannot.
gene_phenotype_detail, because the concordance count must exclude All and
non_EUR, which pool the same individuals as the strata being counted: the
obvious SQL double-counts and looks entirely reasonable.
variants, because the variant-level release is a separate upstream format, an
order of magnitude larger and rebuilt often enough that a local copy would be
stale within the week.
schema(), because a syntactically perfect query can still be scientifically
wrong here. 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, and a p-value of exactly zero is the strongest result rather than
a missing one. Several of those invert an answer instead of degrading it, which
is why they travel with the columns rather than sitting in a README.
The database
873 MB, published as a
release asset and
downloaded once into ~/.cache/brava-mcp/ at first use. Deliberately not
committed: deployments reset the clone on every spawn, so a gigabyte inside it
would be re-fetched forever. 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).
betaandsealways come from the inverse-variance-weighted Burden meta-analysis, including on rows where you readp_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
synonymousmask 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.
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