NUDT15*8 is assigned decreased function based on limited evidence. One patient genotyped NUDT15*2/*8 was extremely sensitive to thiopurine treatment (28659275). An in vitro study using a bacterial expression system found that NUDT15.8 exhibits decreased enzymatic activity and decreased protein thermostability compared to NUDT15.1 (28659275). An additional in vitro study expressed NUDT15*8 in HEK293 cells and found that protein expression and thiopurine sensitivity were comparable to cells expressing NUDT15*1 (32094176). Seven out of nine variant effect predictors tested by CPIC staff predict that the NUDT15*8-defining SNV, c.103A>G (p.K35E), impairs protein function.