As different aspects of phenotypic and genetic heterogeneity in ADPKD are likely due to additional genetic and environmental factors[6], we hypothesised that rare variant burden in the form of rare, additional, potentially protein-altering (RAPPA) variants in PKD1 may contribute to the spectrum of phenotypic variability seen in ADPKD. This evidence concerns the gene PKD1 and autosomal dominant polycystic kidney disease.