AxeCap

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.