SLC6A1 and neurodevelopmental disorder: Our functional data strongly suggest that loss-of-function effects underlie seizures, DD, and ASD phenotypes, excluding the possibility of undiscovered gain-of-function variants and complex genotype-phenotype relationships as explanations for the enrichment for missense variants observed in SLC6A1. We next considered whether PTVs might increase the rate of prenatal lethality leaving a disproportionate number of missense variants in cohorts of children with neurodevelopmental disorders.