White-Sutton syndrome (WHSUS) is a rare, autosomal dominant neurodevelopmental disorder caused by heterozygous loss-of-function alterations in the POGZ gene. WHSUS exhibits variable expressivity, often overlapping with other neurodevelopmental disorders. In this study, we characterized a distinct DNA methylation epigenetic signature (episignature) that differentiates WHSUS from unaffected individuals, as well as from individuals with other neurodevelopmental disorders that also have episignatures, using a cohort of both published and unpublished cases of POGZ haploinsufficiency.