Reliability boundaries of protein language-model zero-shot variant scores: unified-score author-review research release

Abstract

Reliability boundaries of protein language-model zero-shot variant scores: unified-score author-review research release Version: 2026.10.02-author-review. Scientific submission HOLD. Publication of this research artifact does not constitute journal submission, acceptance or independent scientific clearance. Scientific scope: A protein-language-model reliability-boundary atlas with 4,677 identified clinical variant scores across 20 genes. Current discrimination, five-fold out-of-fold calibration and saved identity-grouped refitting records use the same recovered score version. Nonclinical and historical gnomAD/antibody summaries remain explicitly separated. Included files: Current Article and readable SI, full figure/table sources and locked snapshots, 4,677 saved row scores, 4,677 OOF predictions, 5,000 saved refit metric records, reference identity hashes/lengths, scoring and analysis code, no-inference verifier, upstream notices and checksums. Reproduction boundary: The default standard-library verifier checks score identities, AUROC, OOF metrics/bins and saved refit summaries without model forwards, new calibrator fits or network access. Full matching reference sequences, original clinical input files and official model weights are upstream prerequisites and are not bundled. Unrecorded source release/access dates are not invented. Remaining limitations: Author-review/HOLD: no external, gene-disjoint or position-disjoint clinical validation. Historical gnomAD was not newly rescored; archived antibody interval identities remain unresolved. Public availability and byte identity do not attest independent scientific clearance. Public source: https://github.com/PeterPonyu/a3-plm-boundary-atlas, tag author-review-2026-10-02. README, DATA_SOURCES.md, THIRD_PARTY_NOTICES.md and the exact release manifest accompany the ZIP. SHA-256 identities bind the current Article/SI and payload; historical source-capsule contracts remain provenance only. Rights: author-owned code is MIT licensed; author-written text, tables and author-generated result aggregates are CC BY 4.0, to the extent of author rights. Third-party data, labels, source-image portions, structures, method implementations, weights, software and fonts retain upstream conditions and are not relicensed by this record.