Cleft lip and palate is a common birth defect that has a complex etiology resulting from an interaction of genetic and environmental factors. Few genes are known to contribute to its etiology. CHARGE syndrome is a common multiple malformation syndrome in which 20-36% of the cases have clefting. CHARGE is caused by mutations or deletions in the CHD7 gene. We analyzed the coding regions of CHD7 in nine CHARGE cases and identified five mutations, four of which were novel. We sequenced selected CHD7 exons in non-syndromic clefting cases from Iowa and Philippines populations, as well as matched controls. Variants in non-syndromic cases were found, however, the numbers were not statistically different from the controls. Association analysis of three single nucleotide polymorphisms (SNPs) using 878 case-parent triads from Iowa and Philippines population showed no significant overtransmission. Mutations in CHD7 are not common in isolated clefting cases and we found minimal evidence that CHD7 can act as a modifier for non-syndromic clefting.