We have compared the melanogenic activities of cultured melanocytes carrying two common TYR alleles as homozygous 192S-402R wildtype, heterozygous and homozygous variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wildtype strains on average had higher levels of TYR protein and enzyme activity than other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR protein, displayed altered trafficking and glycosylation, with reduced DOPAoxidase. However, near wildtype TYR activity levels could be recovered at lower growth temperature. In a sample population from Southeast Queensland these two polymorphisms were present on four TYR haplotypes, designated as WT 192S-402R, 192Y-402R, 192S-402Q with a double variant 192Y-402Q of low frequency at 1.9%. Based on cell culture findings and haplotype associations, we have used an additive model to assess the penetrance of the ten possible TYR genotypes derived from the combination of these haplotypes.This article is protected by copyright. All rights reserved.