The NM_001204.7(BMPR2) c.1509A>C variant is a missense variant predicted to cause substitution of glutamate by aspartate at amino acid 503 (p.Glu503Asp). The highest population minor allele frequency in gnomAD v2.1.1 (controls) is 0.0001105 (1/9046 alleles) in East Asian population, which is higher than the ClinGen PH VCEP threshold (<0.01%) for PM2 but lower than the threshold (>0.1%) for BS1. Therefore, this variant does not meet either of these population criteria. The computational predictor REVEL gives a score of 0.662, which is neither above nor below the thresholds predicting a damaging or benign impact on BMPR2 function. The variant does not affect protein localization to the plasma membrane (PMID: 25688877) or cell viability (PMID: 30809644). A single luciferase assay demonstrated comparable canonical transcriptional activity to wild-type (PMID: 18321866). However, the lack of effect on canonical signaling in one assay without replication in an independent assay, did not provide conclusive evidence for non-criticality (BS3 not met). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for pulmonary arterial hypertension based on the ACMG/AMP criteria applied, as specified by the ClinGen Pulmonary Hypertension VCEP: No criteria scored. (VCEP specifications version 1.1, 1/18/2024)