The c.391C>T (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of leucine by phenylalanine at amino acid 131 (p.Leu131Phe; legacy nomenclature p.Leu99Phe, Antithrombin Budapest 3 (ATBp3)). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003516 (4/113752 alleles) in the non-Finnish European population, which does not meet criteria for PM2_Supporting (MAF =< 2.0 X 10-5 in gnomAD). The computational predictor REVEL gives a score of 0.853, which is above the threshold of >0.6 and provides evidence that correlates with impact to SERPINC1 function (PP3). The variant has been reported to segregate with AT deficiency in at least 11 affected family members from 2 families (PP1_Strong; PMIDs: 32686144, 24072242). This variant has been reported in at least 100 probands with AT deficiency and is a founder variant in the Hugarian population. Further studies of the Hungarian cohort demonstrated that homozygosity was associated with thrombosis at a younger age and led to a high thrombotic risk while the heterozygous carriers also had venous and/or arterial thrombosis, as well as pregnancy complications. This variant was also reported in internal laboratory data (PS4_Very Strong; PMIDs: 26748602, 1555650, 32686144). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: PP1_strong, PP3, PS4_Very Strong