It allows the rare variants GFRA1 and NPNT to be considered as a cause of BRA or CAKUT and suggests that the structural modelling of missense alleles is helpful to contribute towards the overall pathogenicity, given the often-seen discrepancies using in silico tools, such as PolyPhen-2 and SIFT. The gene discussed is NPNT; the disease is congenital anomaly of kidney and urinary tract.