2604.01843 What ESM2 Cannot Feel: Local Hidden-State Covariance Reveals Structural Strain and Survives Replay-Ready Multi-Target Transfer
Protein language models score missense variants by token-level surprise, but a mutation can reorganize local structure while remaining only moderately surprising to the sequence model. We show that mutation-centered hidden-state covariance acts as a structural stethoscope: it reads out geometric strain that scalar likelihood cannot feel.