Weekly issue 2026-W41 ·
The population frequency of predicted pathogenic variants in the genes associated with Autosomal Dominant Polycystic Liver Disease (ADPLD) and kidney cysts
Plain language
Polycystic liver disease can run in families through changes in at least seven genes, which can also cause a few kidney cysts but rarely kidney failure. Using large public gene databases, researchers estimated that roughly 1 in 91 to 1 in 130 people carry a likely harmful change in one of these genes, more often in some ancestries. Many carriers never develop liver or kidney cysts, so a positive result needs careful interpretation.
Clinical note
gnomAD v2.1.1 (ANNOVAR: LoF, structural/CNV, null and conserved rare damaging missense) and gnomAD v4.1 ClinVar P/LP for GANAB, ALG8, ALG9, PRKCSH, SEC63, LRP5 and SEC61B. Predicted pathogenic carriers ~1 in 91 (v2.1.1) and 1 in 130 (ClinVar); LRP5 and ALG8 (milder phenotypes) most frequent. Higher in admixed American (1/91), Finnish (1/110) and African/African American (1/43) vs European (1/187). Incomplete penetrance and variable expressivity — interpret panel findings with phenotype and family history.
Question for your next visit
If a gene panel finds a variant linked to polycystic liver disease, what does it mean for me and my relatives if we have few or no cysts?