mapped by homology with relatively high confidence. Given the rapidly increasing availability of genomic information and the prevalence of a large number of rare variants differing between individual genotypes, it will be important to have in place facile, inexpensive and rapid screening mechanisms for the functional evaluation of mutations and their potential contribution to autism and other disorders. As more autism-associated variants in NHE genes will be forthcoming, our approach will serve as a template for scoring their potential severity. A similar approach was recently used for p53 mutations, in which structure-driven assessment was used to correctly predict patient outcome47. While such a detailed level of insight is not yet possible in the case of autism, our study represents an important first step toward that goal.