NAT2*7 is assigned decreased function based on definitive evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*7 allele as "slow" and possibly substrate dependent. Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". NAT2*7 is characterized by the core SNVs c.857G>A (p.G286E) and c.803G>A (p.R268K). c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly exhibited increased function in vivo and in vitro. The functional SNV c.857G>A (p.G286E) has been studied for more than 25 years and has shown decreased NAT2 N-acetylation activity in both clinical and in vitro studies using various substrates. Clinical studies have demonstrated that individuals homozygous for NAT2*7 or heterozygous for NAT2*7 in combination with another decreased function allele exhibit decreased acetylation activity toward caffeine metabolites (8102597, 7668286, 9891107, 10744128, 20801937, 22970273, 24221535, 28653770), isoniazid (2376572, 9154882, 9321764, 19336229, 35928262), and sulphonamides (1872889, 15032315, 16570187, 18167504, 21946899). Individuals homozygous for NAT2*7 or heterozygous for NAT2*7 in combination with another decreased function allele exhibit increased hydralazine exposure (24702251, 31257615). In vitro studies have shown that NAT2*7 has decreased N-acetylation activity toward numerous substrates (8081359, 7669073), and NAT2*7 exhibits substrate specificity , exhibiting increased affinity for diaminodiphenyl sulfone (dapsone), sulfamethazine, and sulfapyridine, and decreased affinity for its cofactor, acetyl-CoA as compared to the former reference NAT2*4 (17434923, 33815485, 7669073, 11337936). Nine out of nine variant effect predictors tested by CPIC staff predict that c.857G>A (p.G286E) does not impair protein function. Published in silico modeling predicts that c.857G>A disrupts the size/shape of the protein's active site (18680467), this result combined with the decreased affinity for acetyl-CoA is likely the molecular mechanism for the decreased acetylation activity observed.