Abstract
A recently described method to predict pathogenicity of DNA variants uses a DNA language model and can be applied to both coding and non-coding variants. For coding variants the performance of this method, termed GPN-MSA (genomic pretrained network with multiple-sequence alignment), was reported to be superior to CADD. We compare the performance of this method against 45 other predictors applied to rare coding variants in 18 gene-phenotype pairs. We find that while GPN-MSA produces stronger evidence for association than CADD it is not the best-performing method for any gene and on average other prediction methods are superior. While GPN-MSA may be useful for predicting the pathogenicity of non-coding variants, it would seem sensible for clinicians and researchers to utilise other methods when dealing with coding variants.This research has been conducted using the UK Biobank Resource.