COL4A1 and snowflake vitreoretinal degeneration: Missense variants, typically but not always affecting the glycine residue in the repetitive Gly-X-Y regions, are associated with SVD and ischemic and hemorrhagic subcortical lacunar strokes.22 Variants affecting the C4 domain associated with tropocollagen assembly have also been associated with SVD.23 In 10 individuals (1.1%, 95% CI 0.6%–1.9%), we identified 9 missense COL4A1 variants (figure 2B).