Despite this, p.R174G’s novel perturbation of TREX1′s substrate binding (as opposed to catalysis or localization), the lack of prior biochemistry-pathology corollaries for TREX1-associated SVD with CADASIL-like pattern, the rare allelic frequency, the pathogenicity scores, and the absence of homozygous individuals in all the ethnic groups (Table 1), leave open the possibility of a clinical causality for this variant. Here, TREX1 is linked to snowflake vitreoretinal degeneration.