NAT2*21 is assigned uncertain function based on inadequate evidence. NAT2*21 is characterized by the core SNVs c.458C>T (p.T153I) and c.803G>A (p.R268K). c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly shown normal function in vivo and in vitro. Published in silico modeling of c.458C>T (p.T153I) predicts that this variant impairs protein function based on the exposure of hydrophobic residues that may facilitate protein aggregation and/or targeted protein degradation (19909761). However, eight out of nine variant effect predictors tested by CPIC staff predict that c.458C>T (p.T153I) is neutral for NAT2 protein function and structure-based tools predict that this variant may increase protein stability.