NAT2*46 is assigned decreased function based on definitive evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*46 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". NAT2*46 is characterized by the core SNVc.191G>A (p.R64Q, defining NAT2*14) which has repeatedly shown decreased NAT2 function in numerous in vivo and in vitro studies. NAT2*46 was reported in three individuals in a NAT2 phenotyping study using isoniazid (INH) as a probe drug (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). In vitro studies have shown that NAT2*46 exhibits decreased thermostability and decreased N-acetyltransferase activity toward sulfamethazine and isoniazid compared to the former reference NAT2*4 (10574910, 28523442). Six out of ten variant effect predictors tested by CPIC staff predict that c.191G>A (p.R64Q) impairs protein function. Published in silico modeling predicts that c.191G>A (p.R64Q) decreases protein stability and hinders electrostatic interactions (18680467).