For the first of these groups, the low numbers of pLoFs in UKB may be the result of haploinsufficiency in these genes being genuinely highly penetrant; for example, STXBP1, MED13L, and PURA (in which haploinsufficiency is associated with severe intellectual disability) [26–28] all have > 100 pLoFs in ClinVar but no coding pLoFs in UKB. The gene discussed is STXBP1; the disease is Intellectual disability.