Koenig SN, Sucharski HC, Jose E, et al. - This study was attempted to ascertain whether compound heterozygous variants in SCARB1 cause disease in two brothers with severe, early-onset coronary artery disease (CAD). Researchers have distinguished rare, compound heterozygous variants in SCARB1 that segregate with severe, premature CAD, following patterns of Mendelian inheritance using whole exome sequencing. The findings give the first molecular mechanism to demonstrate the Mendelian inheritance of CAD as a result of human SCARB1 variants. In this family, the rarity of these variants supports pathogenicity. Moreover, it was shown that SR-BI p.G319V, which has previously been reported benign in the context of heterozygosity, was uniquely presented alongside a null allele, indicating the disease-contributing capability of loss-of-function SCARB1 variants within the population.