While several studies have identified multigenerational families with clinically significant phenotypes such as focal segmental glomerulosclerosis, chronic kidney disease (CKD), and KF segregating with monoallelic P/LP COL4A3 or COL4A4 variants, and sequencing studies in unselected kidney disease cohorts recognize these variants as important contributors to kidney disease in the population [14, 15], the absolute risk of KF due to these genetic variants remains poorly understood. This evidence concerns the gene COL4A4 and focal segmental glomerulosclerosis.