NAT2*40 is assigned decreased function based on definitive evidence. NAT2*40 is characterized by the core SNV c.857G>A (p.G286E, defining NAT2*7) which exhibits decreased N-acetylation activity toward sulfamethazine, decreased thermostability, and decreased protein expression in a mammalian cell lines compared to NAT2*4 (17434923). NAT2*40 also exhibits decreased protein levels when expressed in yeast cells (11337936). A clinical NAT2 phenotyping studying using isoniazid (INH) as a probe drug identified 2 patients carrying NAT2*40 (28959610). These individuals were classified among slow acetylators, who exhibited an acetylation index (defined as the ratio of plasma INH concentration at the 3rd hour, in mg/L + 0.6 divided by the dose in mg/kg) below that of rapid acetylators, which were defined as individuals homozygous for NAT2 increased function alleles *1 or *4 (28959610). Nine out of nine variant effect predictors tested by CPIC staff predict that c.857G>A (p.G286E) does not impair protein function. However, published in silico modeling indicates that c.857G>A (p.G286E) disrupts the size/shape of the protein's active site (18680467).