In the case of genetically unsolved recessive cystic kidney diseases such as nephronophthisis, the finding of one variant which affects function, such as a heterozygous nonsense variant in a known genetic cause of the disease (e.g. NPHP1), should prompt a review of synonymous variants within the same gene to see if a synonymous variant may be the second allele which affects function. The gene discussed is NPHP1; the disease is cystic kidney disease.