Coexisting mutations could have additive or synergistic effects on disease expression: FLNA variants could promote vascular abnormalities alongside Arg4810Lys; NOTCH3 mutations combined with Arg4810Lys lead to more severe cerebrovascular disease; and PCSK9 variants influence the cardiovascular phenotypes that modify Arg4810Lys-related vascular risk. This evidence concerns the gene PCSK9 and cerebrovascular disorder.