NAT2*33 is assigned decreased function based on moderate evidence. NAT2*33 is characterized by the core SNVs c.341T>C (p.I114T, defining NAT2*5) and c.472A>C (p.I158L). Published in silico modeling predicts that c.472A>C (p.I158L) does not alter NAT2 protein function (19164093, 19909761). Similarly, ten out of ten variant effect predictors tested by CPIC staff predict that c.472A>C (p.I158L) is neutral/tolerated for NAT2 function. Thus, NAT2*33 is assigned decreased function based on c.341T>C (p.I114T) . c.341T>C (p.I114T) defines NAT2*5 which has repeatedly shown decreased NAT2 function 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*33 would presumably be degraded in the same manner. Five out of ten variant effect predictors tested by CPIC staff predict that c.341T>C (p.I114T) impairs protein function. While.472A>C is not predicted to impair protein function, it remains unknown whether there are any combinatorial effects associated with c.341T>C and c.472A>C.