Consistent identification of a common, nonsynonymous risk allele (MTHFD1 NM_005956.4:c.1958G > A; R653Q) in methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1) provides evidence linking purine synthesis to NTD risk. The gene discussed is MTHFD1; the disease is neural tube defect.