Article

Coupling codon and protein constraints decouples drivers of variant pathogenicity

2025-03-14

Abstract excerpt

Predicting the functional impact of genetic variants remains a fundamental challenge in genomics. Existing models focus on protein-intrinsic defects yet overlook regulatory constraints embedded within coding sequences. Here, we couple a codon language model (CaLM) with a protein language model (ESM-2) to dissect the drivers of variant pathogenicity. On ClinVar data, both modalities contribute near-equally to disti...

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Literature Corpus work: 84626e05-bfbc-576d-9249-57539616848a
DOI: 10.1101/2025.03.12.642937

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