NT5E and craniosynostosis: Although the Xenopus assay supports the genetic evidence that the c.1198G>C (p.Gly400Arg) substitution is causative of the phenotype in family 5, a cautionary note is provided by the finding that p.Thr414Ala also disrupted en-2 expression, because this variant occurs too frequently (at 1 in 1,167 alleles) to be penetrant for craniosynostosis in more than a small proportion of individuals who carry this variant.