Residual allelic activity likely underlies the low rates of disease expression for predicted loss-of-function variants in population-scale biobanks

Loss-of-function variants in genes linked to haploinsufficient Mendelian diseases have unexpectedly low rates of phenotypic expression in population-scale biobanks. Using statistical modeling and machine learning, we demonstrate that many of these variants likely harbor residual allelic activity, allowing them to remain unexpressed in many individuals.