This single-base substitution might cause an impact on CRD of FZD4, and lead to disrupted interaction between CRD and its ligands, further resulting in Wnt signaling dysfunction and retinal vascular alternations; All the structural or functional changes, combined with the absence of the FZD4 variant in databases, indicate its pathogenicity in ROP. This evidence concerns the gene FZD4 and retinopathy of prematurity.