In the case of nonsyndromic midline craniosynostosis due to pathogenic rare variants in SMAD6, low penetrance (< 60%) is observed with SMAD6 variation alone, but 82% (14/17) of affected individuals had an additional, common BMP2 allele, demonstrating digenic inheritance of 2 unlinked loci, in this case with one rare variant and one common SNV [33]. The gene discussed is SMAD6; the disease is craniosynostosis.