NAT2*32 is assigned decreased function based on moderate evidence. NAT2*32 is characterized by the core SNVs c.203G>A (p.C68Y) and c.341T>C (p.I114T). An in vitro study showed that substituting a glycine in place of cysteine at position p.68 abolished NAT2 N-acetyltransferase activity toward sulfamethazine, procainamide, p-aminosalicylic acid, and 2-aminofluorene; the authors discuss the high probability that p.Cys68 lies within the NAT2 active site and is directly involved in acetyl transfer (1559981). An additional in vitro study found that NAT2 p.C68A exhibited undetectable N-acetyltransferase activity toward p-aminosalicylic acid and sulfamethazine (9173883). Thus, substitution of a tyrosine in place of cysteine at residue p.68 would likely abolish NAT2 enzymatic activity. Published in silico modeling predicts that c.203G>A (p.C68Y) alters the NAT2 catalytic mechanism, rendering the protein non-functional (19909761). Lastly, nine out of ten variant effect predictors tested by CPIC staff predict that c.203G>A (p.C68Y) impairs protein function. c.341T>C (p.I114T) defines NAT2*5, which has repeatedly shown decreased NAT2 acetylation activity in numerous in vivo and in vitro studies. Additionally, an in vitro study showed that NAT2*5 is subjected to enhanced protein degradation by the proteasome (15564878). Thus, NAT2*32 would presumably be degraded in the same manner. While the committee agreed to the assignment of decreased function based on the function of c.341T>C (p.I114T), there was a lack of consensus regarding the function of c.203G>A (p.C68Y). It remains unknown whether there are any combinatorial effects associated with c.341T>C and c.203G>A.