AxeCap
The user I built for is a genetic counselor holding a variant of uncertain significance in a regulatory region.
Core trick
Scores each variant across five evidence sources with a visible deterministic points rule, while Claude only reconciles and explains the ranked results.
Description
The user I built for is a genetic counselor holding a variant of uncertain significance in a regulatory region. Roughly 40% of what a clinical exome returns is uncertain, and the noncoding ones tend to stay that way forever, because the ACMG classification rules were written for coding variants and mostly do not apply.
VUS Copilot takes a variant, or a whole VCF straight from a sequencing pipeline, and checks it against five real sources at once: RegulomeDB, Ensembl VEP, Open Targets with ClinVar, gnomAD, and a Myint et al. 2020 MPRA, which is an actual wet lab measurement rather than a prediction. Deterministic code ranks the cohort and shows every point it awarded. Claude reconciles the evidence and explains it in plain language.
The interesting part is what happens when the sources disagree. In our demo cohort the CFTR 3849+10kb variant is Pathogenic by ClinVar practice guideline, and yet RegulomeDB ranks it a 4 and Ensembl VEP sees no regulatory feature at all. The predictors miss a known pathogenic variant. Going the other way, variants the wet lab confirms are held out of the worklist by ACMG BA1 once you notice that 40 to 87% of people carry them.
All of it is auditable. A reproducible grounding benchmark ships with 64 fabricated claims the audit has to catch, and it names the 7 it still misses.
README excerpt
# VUS Copilot **Decision-support for interpreting variants of uncertain significance (VUS) in regulatory, non-coding regions of the genome.** Give it one variant, or drop in a whole VCF. VUS Copilot checks every variant against five evidence sources in parallel, ranks the list with a deterministic, fully-visible triage score, and uses Claude as a reasoning layer that **reconciles** the evidence into a clinician-readable, **fully-cited** report. It targets the gap where coding-variant interpretation is mature but regulatory interpretation is not: the evidence is scattered, and most variants land in "uncertain significance" by default. The architecture is **code ranks, Claude explains.** The ranking is deterministic, so it is reproducible and auditable, and the model cannot move a row. Claude reads the finished ranking and writes the summary on top of it. > ⚕️ **Triage / decision-support assistant, not a diagnostic tool.** For genetic counselors > and clinical geneticists to prioritize and contextualize regulatory VUS, not to make > clinical calls. Every conclusion traces to a real source, not model authority. Built for **[Built with Claude: Life Sciences](https://cerebralvalley.ai/e/built-with-claude-life-sciences)** (Anthropic × Cerebral Valley × Gladstone Institutes), Builder Track. --- ## Two ways in **One variant** (`chr`/`pos`/`ref`/`alt` or an rsID) gives you the full source-cited report: what each source said, where they agree, where they conflict, and what is s