This variant segregated with disease in a proband containing three affected individuals (patient, mother, and maternal uncle, all heterozygous). One additional unrelated patient was also heterozygous. This variant was not seen in >100 genomes tested. While cysteine residues are usually involved in CADASIL, this residue is highly conserved and there is a mutation cluster around this site. The LOD score for this family is 0.9.