NAT2*14 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*14 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". ". NAT2*14 is characterized by the core SNVs c.191G>A (p.R64Q) 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.191G>A (p.R64Q) 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 demonstrate that individuals homozygous for NAT2*14 or heterozygous for NAT2*14 in combination with another decreased function allele exhibit decreased acetylation activity toward caffeine metabolites (8102597, 7668286, 9110365, 9565293, 21750470, 24221535, 28653770), isoniazid (9154882, 17505821), sulfamethazine (21946899), and dapsone (10762005). Six out of nine variant effect predictors tested by CPIC staff predict that c.191G>A (p.R64Q) impairs protein function. Published in silico modeling predicts that c.191G>A decreases protein stability and hinders electrostatic interactions (18680467). In vitro studies have demonstrated that NAT2*14 exhibits decreased protein expression and thermostability compared to the former reference, NAT2*4 (11337936, 17434923, 8081359).