Calibration of additional computational tools expands ClinGen recommendation options for variant classification with PP3/BP4 criteria.

We previously developed an approach to calibrate computational tools for clinical variant classification, updating recommendations for the reliable use of variant impact predictors to provide evidence strength up to Using our local posterior probability-based calibration and our established data set of ClinVar pathogenic and benign variants, we determined the strength of evidence provided by three new tools (AlphaMissense, ESM1b, VARITY) and calibrated scores meeting each evidence strength. Results All three tools reached the At calibrated thresholds, three new computational predictors provided evidence for variant pathogenicity at similar strength to the four previously recommended predictors (and comparable with functional assays for some variants). This calibration broadens the scope of computational tools for application in clinical variant classification. Their new approaches offer promise for future advancement of the field.