The NM_000020.3: c.1232G>A variant in ACVRL1 is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 411 (p.Arg411Gln). The overall minor allele frequency in gnomAD v2.1.1 is 0.000007980 (2/250642 alleles), which is lower than the ClinGen Hereditary Hemorrhagic Telangiectasia VCEP threshold (<6 total alleles) for PM2_Supporting, meeting this criterion (PM2_Supporting). This variant has been reported in >10 probands with a phenotype consistent with HHT (PS4; PMID: 8640225, 31400083, 32300199, Internal lab contributors). At least one patient's phenotype meets Curacao Criteria for HHT, and sequencing and large deletion/duplication analysis was performed for ENG and ACVRL1, which is highly specific for HHT (PP4_Moderate; PMID: 32300199). The variant has been reported to segregate with HHT in 8 affected family members from one family (PP1_Strong; PMID: 8640225). The computational predictor REVEL gives a score of 0.904, which is above the threshold of ≥0.644, evidence that correlates with impact to ACVRL1 function (PP3). Additionally, binding assays in cell lines showed no BMP9 response indicating that this variant impacts protein function (PS3_Supporting; PMID: 20501893). In summary, this variant meets the criteria to be classified as pathogenic for autosomal dominant hereditary hemorrhagic telangiectasia based on the ACMG/AMP criteria applied, as specified by the ClinGen Hereditary Hemorrhagic Telangiectasia Variant Curation Expert Panel: PS4, PP1_Strong, PP4_Moderate, PM2_Supporting, PP3, PS3_Supporting (specification version 1.0.0; 1/4/2024).