This variant, which has a 3.4% allele frequency in 1000 genomes data, is reported to be associated with autoimmune disease when homozygous. Because multiple hypotheses are effectively tested the significance of the case/control data is unclear. Assuming it is pathogenic, the small sample size (due to variant rarity) means that it is unclear to what extent the variant increases relative risk.
Surolia, I. et al. Nature advance online publication doi:10.1038/nature09115 (2010). — This paper implicates this polymorphism as potentially contributing to autoimmune diseases when homozygous. The variant was seen homozygously in 8 out of 923 cases and 0 out of 648 controls. Using two-tailed Fisher’s Exact, this is p = 0.024. However, because there are several other polymorphisms, multiple hypotheses were implicitly being tested and so we give this a case/control significance of 1 point (0.1 < p < 0.05). The overall allele frequency of the variant in controls is 0.049, they list four other variants with allele frequencies > 0.025.
They report that the protein product with this variant is catalytically active but is not secreted. This finding was reproduced in a pulse-chase experiment with 35S-methionine.