NM_000138.5 c.3707G>A is a missense variant in FBN1 predicted to cause a substitution of a cysteine by tyrosine at amino acid 1236 (p.Cys1236Tyr). This variant has been identified in at least three individuals including two probands with clinical diagnoses of Marfan syndrome, with neonatal onset in one case, and one proband with a highly specific Marfan syndrome phenotype including thoracic aortic aneurysm and dissection (TAAD), ectopia lentis, and systemic features of Marfan syndrome (PS4_moderate, PP4; UZG, Mayo, & Bichat internal data). It is not present in gnomAD (PM2_supporting; https://gnomad.broadinstitute.org/ v2.1.1 & v3.1.2). 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 support that this variant is likely to impact the protein (PP3; REVEL = 0.960). The constraint z-score for missense variants affecting FBN1 is 5.06 (PP2). In summary, this variant meets criteria to be classified as pathogenic for Marfan syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: PM1_strong, PS4_moderate, PP2, PP3, PP4, PM2_supporting.