The fact that no further recessive missense mutations of VWA2 were detected when examining another ~1,000 individuals with CAKUT is not surprising, given that the Arg466Cys mutation most likely represents a specific dose-dependent neomorphic mutation that affects intra- and/or intermolecular disulfide bond formation, thereby creating a protein with novel and harmful biochemical properties and functions. Here, VWA2 is linked to congenital anomaly of kidney and urinary tract.