6/ RaCoon performs multicalibration of ESM1b, producing reliable probabilities across all relevant subgroups using minimal supervision.

5/ This motivated RaCoon (Residue-aware calibration via conditional distributions).
(It calibrates like a raccoon sorts trash: by categories. 😉)

4/ Surprisingly calibrating per variant subgroup (i.e. interface) not only improves miscalibration but also increase global AUROC across most models.

3/ We calibrate VEPs at the residue level since variant effects depend strongly on local residue properties. We find that model entropy distribution can guide calibration.

2/ In a calibrated model a model score of 0.8 means ~80% of similar variants are pathogenic. But VEPs often fail, especially for variants in disordered regions or protein-protein interfaces.