NAT2*31 is assigned decreased function based on moderate evidence. NAT2*31 is characterized by the core SNVs c.70T>A (p.L24I) and c.341T>C (p.I114T). Published in silico modeling predicts that c.70T>A (p.L24I) does not impair NAT2 protein function (19909761). However, five out of ten variant effect predictors tested by CPIC staff predict that c.70T>A (p.L24I) impairs protein function and structure-based predictors suggest that c.70T>A (p.L24I) decreases protein stability which could lead to decreased function. c.341T>C (p.I114T, defining NAT2*5) has repeatedly shown decreased NAT2 N-acetylation activity in numerous in vivo and in vitro studies and five out of ten variant effect predictors tested by CPIC staff predict that c.341T>C (p.I114T) impairs protein function. Additionally, an in vitro study showed that NAT2*5 (which contains the core SNV c.341T>C, p.I114T) is subjected to enhanced protein degradation by the proteasome (15564878). Thus, NAT2*31 would presumably be degraded in the same manner and is assigned decreased function based on the function of c.341T>C (p.I114T). Despite this, it remains unknown whether c.70T>A has any combinatorial effects with c.341T>C.