Variant-effect predictor benchmarking against DMS

The core user question: "I have a variant-effect predictor — does it actually correlate with experimental DMS measurements on this protein?"

The predictor can be anything that assigns a numeric score to single missense variants:

• ESM-C 6B Sparse Autoencoder (SAE) feature drops at the mutation site
• AlphaMissense pathogenicity scores
• ESM logits-based variant scoring (ESM_score_sequence)
• EVE / EVE++ scores
• Conservation scores (ConSurf, Rate4Site)
• DynaMut2 ΔΔG predictions
• A custom in-house model

This skill validates ALL of these against a DMS dataset with the same statistical framework. SAE is shown as the worked example because the surrounding skills in this collection are SAE-themed, but the procedure is predictor-agnostic.