Among the variants, seven are in known PAH risk genes: four in TBX4, two in BMPR2, and one in ACVRL1. Excluding these known risk genes, there are 22 LGD + D-Mis variants in genes highly expressed in developing heart and lung, still significantly more than expected (enrichment rate = 1.86, p = 0.008, 10 expected risk variants). This evidence concerns the gene ACVRL1 and pulmonary arterial hypertension.