NM_000138.5 c.7409G>T is a missense variant in FBN1 predicted to cause a substitution of a cysteine by phenylalanine at amino acid 2470 (p.Cys2470Phe). This variant was found in a proband with thoracic aortic aneurysm (TAA) and a systemic score ≥7 which is a specific phenotype that satisfies the revised Ghent criteria for a clinical diagnosis of Marfan syndrome (MFS) (PP4; PMID: 38374194). This variant has been reported 3 times in ClinVar as pathogenic (1) likely pathogenic (1), and of uncertain significance (1) (Variation ID: 1098776 ). It has been identified in a proband who does not meet diagnostic criteria for MFS but has TAA and several systemic features of MFS (Invitae internal data). This variant is not present in gnomAD (PM2_supporting; https://gnomad.broadinstitute.org/). This variant affects a cysteine residue in a calcium-binding EGF-like domain; cysteine residues are involved in the formation of disulfide bridges which are essential for the protein structure (PM1_strong). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3; REVEL = 0.989). The constraint z-score for missense variants affecting FBN1 is 8.2 (PP2; gnomAD v4.1.0). 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, PP2, PP3, PP4, PM2_supporting.