The scientific team classified approximately 17,000 missense coding variants of the LDLR gene, which is the main genetic factor in familial hypercholesterolemia (FH).[1][2] These variants interfere with the breakdown of LDL cholesterol and increase the risk of premature atherosclerosis.[1][2] The study tested the effect of the variants on the amount of LDLR on the cell surface and on LDL uptake, creating sequence-function maps.[2] Functional scores have been correlated with manifestations of hyperlipidemia in human cohorts and improved polygenetic scores for better risk estimation.[1][2] The resource makes it possible to classify almost half of the hitherto unclassified clinical variants of LDLR.[2] This resource accelerates the diagnosis of FH and improves patient outcomes.[1][2] Variants in LDLR account for about 80% of molecularly diagnosed cases of heterozygous FH.[1] New unclassified variants appear frequently in the clinic, and this resource can increase the number of diagnoses up to tenfold.[1]