Our study integrated sequence-basedand structure-based methodsto identify whether specific missense mutants in the PDGF/VEGF domainof VEGFA protein have pathological significance, potentially contributingto rheumatoid arthritis, cancer, and congenital heart disease., The two most significant mutants (R262Q and C266Y) were selectedfor further analysis according to the combination of different computationalalgorithms. Here, VEGFA is linked to congenital heart disease.