NAT2*39 is assigned decreased function based on moderate evidence. NAT2*39 is characterized by the core SNVs c.590G>A (p.R197Q), c.803G>A (p.R268K), and c.838G>A (p.V280M). c.803G>A (p.R268K) defines NAT2*4, formerly considered the reference allele, which has repeatedly shown increased function in vivo and in vitro. Published in silico modeling predicts that c.838G>A (p.V280M) impairs protein function based on the exposure of hydrophobic residues that may facilitate protein aggregation and/or targeted protein degradation (19909761). NAT2*39 was identified in one patient (genotyped NAT2*4/*39) in a NAT2 phenotyping study using isoniazid. This patient was classified as an intermediate acetylator and this study showed lower acetyl-INH/INH ratios for intermediate acetylators compared to rapid acetylators, defined as individuals homozygous for NAT2 increased function alleles *1 or *4 or heterozygous NAT2*1/*4 (24533708). Four out of nine variant effect predictors tested by CPIC staff predict that c.838G>A (p.V280M) impairs protein function, which is supported by published in silico predictions (27984508). c.590G>A (p.R197Q) defines NAT2*6 which has been extensively studied, exhibiting decreased N-acetyltransferase activity both in vivo and in vitro. Similarly, seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A impairs protein function. Thus, NAT2*39 is assigned decreased function based on c.590G>A. Despite this, it remains unknown whether there are any combinatorial effects associated with c.838G>A and c.590G>A.