Anterior segment dysgenesis (ASD) comprises a wide spectrum of developmental conditions affecting the cornea, iris, and lens, which may be associated with abnormalities of other organs. To identify disease-causing variants, we performed exome sequencing in 24 South Florida families with ASD. We identified 12 likely causative variants in 10 families (42%), including single nucleotide or small insertion−deletion variants in B3GLCT, BMP4, CYP1B1, FOXC1, FOXE3, GJA1, PXDN, and TP63, and a large copy number variant involving PAX6. Four variants were novel. Each variant was detected only in one family. Likely causative variants were detected in 1 out of 7 black and 9 out of 17 white families. In conclusion, exome sequencing for ASD allows us to identify a wide spectrum of rare DNA variants in South Florida. Further studies will explore missing variants, especially in the black communities.