The NM_00138 c.6032G>A is a missense variant in FBN1 predicted to cause a substitution of a cysteine by tyrosine at amino acid 2011 (p.Cys2011Tyr). This variant has been reported four times in ClinVar: once as pathogenic, twice as likely pathogenic, and once as uncertain significance (Variation ID: 263898). At least two probands with clinical features of Marfan syndrome carry the same variant (internal lab data, PS4_Sup). This variant is not present in gnomAD (PM2_sup; https://gnomad.broadinstitute.org/v2.1.1). This variant affects a cysteine residue in a calcium binding EGF-like domain. Cysteine residues in these domains are believed to be involved in the formation of disulfide bridges which are essential for the protein structure (PM1_strong). Other missense variants disrupting the Cysteine at this position, (i.e. p.Cys2011Arg and p.Cys2011Ser), have been reported in individuals with features of Marfan syndrome (PMID 29907982, 31163209). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (REVEL: 0.921, PP3). The constraint z-score for missense variants affecting FBN1 is 5.06 (PP2). In summary, this variant meets criteria to be classified as likely pathogenic for Marfan syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: PM1_Strong, PS4_Sup, PM2_Sup, PP2, PP3