CYP2B6*9 (c.516G>T, p.Q172H/splice defect) - Decreased function: CYP2B6*9 is assigned decreased function. When c.516G>T occurs alone, it defines CYP2B6*9. The c.516G>T variant causes aberrant splicing (14551287, 18171905, 24260284) and is in high linkage disequilibrium with c.785A>G, which is part of the CYP2B6*6 haplotype. c.516G>T is also present in several other haplotypes (e.g., CYP2B6*7, *13, *19, *20, *26, *34, *36, *37 and *38). These haplotypes make it difficult to ascertain the presence of *9 and its clinical function. Although several studies have reported a significant association between c.516G>T and efavirenz exposure (over 3-fold increase) in patient plasma and/or hair samples (15622315, 22927450, 23080225), these associations were erroneously attributed to CYP2B6*9 rather than *6. Several in vitro studies using cDNA expression systems show that CYP2B6*9 decreases activity towards efavirenz, bupropion, methadone, ketamine, and nicotine (21659470, 30085944, 30906561, 32238417, 35538637), while others have shown no or increased activity (11243870, 30201214). This discrepancy is probably due to differences in the in vitro expression systems and substrates used. At present, functional information is informed by the fact that alleles with c.516G>T (e.g., CYP2B6*6) have been associated with decreased function (see description for CYP2B6*6 allele). Therefore, consensus among experts was decreased function based on strong evidence.