Pervasive ancestry bias in variant effect predictors

Computational variant effect predictors (VEPs) are playing increasingly important roles in the interpretation of human genetic variants. We observe striking differences in the ways that many VEPs score variants from European compared to non-European populations. We advocate for the adoption of population-free VEPs, i.e. those not trained on human population or clinical variants, to improve health equity and enhance the accuracy of genetic diagnoses across diverse populations.