The SMAD9 c.1117G>A (p.Val373Ile) variant detected in an HPAH case in this study is predicted to be deleterious by in silico analysis, further supported by familial co-segregation and its location with the C-terminal Mad Homology 2 (MH2) domain, a region of extensive evolutionary conservation. This evidence concerns the gene SMAD9 and heritable pulmonary arterial hypertension.