CYP1A2 (Cytochrome P450 1A2) variants and mutations
CYP1A2 (also known as Cytochrome P450 1A2) is a human protein-coding gene encoding a cytochrome P450 1A2 protein. It metabolizes caffeine and many clinically used or environmental compounds in the liver. Genetic variation, smoking, diet, and interacting drugs can substantially change its activity and therefore alter exposure to substrates such as clozapine and theophylline. This analysis covers 1,023 CYP1A2 variants and mutations. Of these, 86% have computational variant effect predictions. Disease context includes hypertensive disorder, osteoarthritis, and essential hypertension. Example CYP1A2 variants include A2T, A2E, and A2A.
Variant analysis overview
- Gene: CYP1A2
- Protein: Cytochrome P450 1A2
- UniProt accession: P05177
- Organism: Homo sapiens
- Variants analyzed: 1023
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 627 unspecified-consequence records; 173 missense variants; 169 synonymous variants; 8 stop-gained variants; 33 frameshift variants; 6 in-frame deletions; 3 splice-region variants; 4 substitution
- Prediction scores: 881 variants have prediction scores (86% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypertensive disorder, osteoarthritis, essential hypertension, coffee consumption, hearing loss disorder, Increased blood pressure, arthritic joint disease, arthropathy, cardiovascular disorder, scleritis, osteoarthritis, hip, Abnormal urine sodium concentration.
Protein structure and variant hotspots
- Protein features: 2 binding sites; 1 post-translational modification sites.
- PTM context: 3 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable CYP1A2 variants
Examples include A2T, A2E, A2A, L3F, L3S, S4F, S4S, Q5L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2T (p.Ala2Thr), gnomAD 15-74749742-G-A, REVEL 0.09, CADD 7.90
- A2E (p.Ala2Glu), gnomAD 15-74749743-C-A, REVEL 0.19, CADD 18.00
- A2A (p.Ala2Ala), gnomAD 15-74749744-A-G, CADD 1.48
- L3F (p.Leu3Phe), ExAC rs758501844, gnomAD rs758501844, REVEL 0.05, CADD 1.55
- L3S (p.Leu3Ser), ExAC rs201871401, TOPMed rs201871401, gnomAD rs201871401, REVEL 0.18, CADD 17.70
- S4F (p.Ser4Phe), TOPMed rs2063304702
- S4S (p.Ser4Ser), gnomAD 15-74749750-C-G, CADD 3.22
- Q5L (p.Gln5Leu), TOPMed rs2063304716, REVEL 0.07, CADD 6.98
- Q5P (p.Gln5Pro), gnomAD 15-74749752-A-C, REVEL 0.10, CADD 5.63
- S6P (p.Ser6Pro), gnomAD rs1253621868, REVEL 0.13, CADD 0.02
- S6T (p.Ser6Thr), gnomAD rs1253621868
- S6Y (p.Ser6Tyr), ExAC rs764359866, gnomAD rs764359866, REVEL 0.05, CADD 0.00
- V7A (p.Val7Ala), TOPMed rs1193278468, gnomAD rs1193278468, REVEL 0.07, CADD 1.60
- V7F (p.Val7Phe), gnomAD 15-74749757-G-T, REVEL 0.10, CADD 4.30
- P8H (p.Pro8His), gnomAD rs1477139859, REVEL 0.17, CADD 18.20
- P8L (p.Pro8Leu), NCI-TCGA Cosmic COSV5965, gnomAD rs1477139859, REVEL 0.08, CADD 14.50, Variant assessed as somatic; moderate impact.
- P8S (p.Pro8Ser), rs751760377, ClinGen CA7659663, NCI-TCGA Cosmic COSV1006, ClinVar RCV004151903, REVEL 0.05, CADD 2.10, Uncertain significance, not specified
- P8T (p.Pro8Thr), gnomAD 15-74749760-C-A, REVEL 0.11, CADD 9.02
- P8P (p.Pro8Pro), gnomAD 15-74749762-C-T, CADD 3.02
- F9F (p.Phe9Phe), gnomAD 15-74749765-C-T, CADD 5.09
- S10L (p.Ser10Leu), ESP rs372412769, ExAC rs372412769, TOPMed rs372412769, gnomAD rs372412769, REVEL 0.21, CADD 13.40
- S10* (p.Ser10Ter), gnomAD 15-74749767-C-A, CADD 33.00
- S10S (p.Ser10Ser), rs781571873, gnomAD 15-74749768-G-A, CADD 0.11
- A11S (p.Ala11Ser), gnomAD rs1471159041, REVEL 0.08, CADD 7.51
- A11T (p.Ala11Thr), gnomAD 15-74749769-G-A, REVEL 0.19, CADD 12.20
- A11D (p.Ala11Asp), gnomAD 15-74749770-C-A, REVEL 0.31, CADD 13.30
- E13G (p.Glu13Gly), ExAC rs756588544, gnomAD rs756588544, REVEL 0.36, CADD 23.10
- E13E (p.Glu13Glu), rs1653592245, gnomAD 15-74749777-G-A, CADD 6.50
- L14P (p.Leu14Pro), NCI-TCGA Cosmic COSV1006, Variant assessed as somatic; moderate impact.
- L14R (p.Leu14Arg), rs1401787029, NCI-TCGA Cosmic COSV1006, gnomAD rs1401787029, REVEL 0.48, CADD 24.50, Variant assessed as somatic; moderate impact.
- L14I (p.Leu14Ile), gnomAD 15-74749778-C-A, REVEL 0.11, CADD 11.90
- L15F (p.Leu15Phe), 1000Genomes rs60086777, ESP rs60086777, ExAC rs60086777, TOPMed rs60086777, REVEL 0.49, CADD 21.80
- L16P (p.Leu16Pro), gnomAD 15-74749785-T-C, REVEL 0.65, CADD 25.20
- L16L (p.Leu16Leu), rs747676615, gnomAD 15-74749786-G-A, CADD 8.79
- A17T (p.Ala17Thr), gnomAD 15-74749787-G-A, REVEL 0.14, CADD 22.90
- A17P (p.Ala17Pro), gnomAD 15-74749787-G-C, REVEL 0.57, CADD 24.70
- A17D (p.Ala17Asp), gnomAD 15-74749788-C-A, REVEL 0.53, CADD 22.70
- A17A (p.Ala17Ala), gnomAD 15-74749789-C-A, CADD 7.04
- S18C (p.Ser18Cys), rs17861152, UniProt VAR 023196, 1000Genomes rs17861152, ESP rs17861152, REVEL 0.21, CADD 19.90
- S18F (p.Ser18Phe), 1000Genomes rs17861152, ESP rs17861152, TOPMed rs17861152, gnomAD rs17861152, REVEL 0.09, CADD 12.90
- S18Y (p.Ser18Tyr), 1000Genomes rs17861152, ESP rs17861152, TOPMed rs17861152, gnomAD rs17861152
- S18P (p.Ser18Pro), gnomAD 15-74749790-T-C, REVEL 0.37, CADD 17.70
- S18A (p.Ser18Ala), gnomAD 15-74749790-T-G, REVEL 0.03, CADD 7.78
- S18S (p.Ser18Ser), rs928955781, gnomAD 15-74749792-T-C, CADD 3.91
- A19P (p.Ala19Pro), TOPMed rs1047643383
- A19T (p.Ala19Thr), NCI-TCGA TCGA novel, REVEL 0.07, CADD 3.06, Variant assessed as somatic; moderate impact.
- A19V (p.Ala19Val), ExAC rs771691950, gnomAD rs771691950, REVEL 0.07, CADD 3.89
- A19H (p.Ala19His), rs746300395, gnomAD 15-74749791-CTG-C, CADD 17.00
- A19D (p.Ala19Asp), gnomAD 15-74749794-C-A, REVEL 0.18, CADD 18.00
- A19A (p.Ala19Ala), gnomAD 15-74749795-C-A, CADD 5.69
- I20M (p.Ile20Met), ExAC rs773045980, TOPMed rs773045980, gnomAD rs773045980, REVEL 0.19, CADD 23.00
- I20V (p.Ile20Val), gnomAD 15-74749796-A-G, REVEL 0.08, CADD 0.10
- I20I (p.Ile20Ile), gnomAD 15-74749798-C-A, CADD 8.02
- F21L (p.Phe21Leu), rs56160784, UniProt VAR 008349, ExAC rs56160784, TOPMed rs56160784, REVEL 0.35, CADD 22.80, Benign, in allele CYP1A2*2
- F21Y (p.Phe21Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in allele CYP1A2*2
- F21C (p.Phe21Cys), gnomAD 15-74749800-T-G, REVEL 0.55, CADD 25.40
- C22Y (p.Cys22Tyr), gnomAD rs1330830770, REVEL 0.18, CADD 21.80
- C22F (p.Cys22Phe), gnomAD 15-74749803-G-T, REVEL 0.16, CADD 21.90
- C22* (p.Cys22Ter), gnomAD 15-74749804-C-A, CADD 31.00
- C22C (p.Cys22Cys), rs2063305061, gnomAD 15-74749804-C-T, CADD 5.32
- L23V (p.Leu23Val), gnomAD 15-74749805-C-G, REVEL 0.31, CADD 15.60
- L23M (p.Leu23Met), gnomAD 15-74749805-C-A, REVEL 0.42, CADD 16.50
- L23P (p.Leu23Pro), gnomAD 15-74749806-T-C, REVEL 0.72, CADD 25.00
- L23Q (p.Leu23Gln), gnomAD 15-74749806-T-A, REVEL 0.61, CADD 24.90
- L23L (p.Leu23Leu), gnomAD 15-74749807-G-A, CADD 2.79
- V24Y (p.Val24Tyr), gnomAD 15-74749806-TG-T, CADD 21.00
- F25C (p.Phe25Cys), ESP rs142454118, ExAC rs142454118, TOPMed rs142454118, gnomAD rs142454118, REVEL 0.34, CADD 23.90
- F25S (p.Phe25Ser), ESP rs142454118, ExAC rs142454118, TOPMed rs142454118, gnomAD rs142454118, REVEL 0.48, CADD 24.00
- F25W (p.Phe25Trp), gnomAD 15-74749811-TTCTG, CADD 24.10
- F25L (p.Phe25Leu), gnomAD 15-74749813-C-A, REVEL 0.11, CADD 12.10
- F25F (p.Phe25Phe), rs1253952551, gnomAD 15-74749813-C-T, CADD 6.06
- W26* (p.Trp26Ter), ExAC rs776313064, gnomAD rs776313064, CADD 36.00
- W26C (p.Trp26Cys), gnomAD 15-74749816-G-C, REVEL 0.42, CADD 24.00
- V27M (p.Val27Met), ExAC rs759309532, TOPMed rs759309532, gnomAD rs759309532, REVEL 0.11, CADD 19.40
- L28I (p.Leu28Ile), rs1263283830, NCI-TCGA Cosmic COSV1006, gnomAD rs1263283830, REVEL 0.04, CADD 0.01, Variant assessed as somatic; moderate impact.
- K29E (p.Lys29Glu), gnomAD 15-74749823-A-G, REVEL 0.15, CADD 15.70
- K29T (p.Lys29Thr), gnomAD 15-74749824-A-C, REVEL 0.13, CADD 6.23
- K29R (p.Lys29Arg), gnomAD 15-74749824-A-G, REVEL 0.08, CADD 0.05
- K29N (p.Lys29Asn), gnomAD 15-74749825-G-C, REVEL 0.11, CADD 4.25
- G30C (p.Gly30Cys), rs765154807, NCI-TCGA Cosmic COSV5966, ExAC rs765154807, TOPMed rs765154807, REVEL 0.19, CADD 12.50, Variant assessed as somatic; moderate impact.
- G30D (p.Gly30Asp), NCI-TCGA Cosmic COSV5966, REVEL 0.13, CADD 2.47, Variant assessed as somatic; moderate impact.
- G30S (p.Gly30Ser), gnomAD 15-74749826-G-A, REVEL 0.04, CADD 0.99
- R32G (p.Arg32Gly), NCI-TCGA Cosmic COSV1006, REVEL 0.17, CADD 5.67, Variant assessed as somatic; moderate impact.
- R32K (p.Arg32Lys), TOPMed rs1244631935, gnomAD rs1244631935, REVEL 0.06, CADD 1.55
- R32M (p.Arg32Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R32R (p.Arg32Arg), gnomAD 15-74749834-G-A, CADD 0.56
- P33H (p.Pro33His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P33R (p.Pro33Arg), ExAC rs775486408, gnomAD rs775486408, REVEL 0.17, CADD 13.30
- P33S (p.Pro33Ser), gnomAD 15-74749835-C-T, REVEL 0.05, CADD 0.01
- P33P (p.Pro33Pro), gnomAD 15-74749837-T-C, CADD 2.96
- R34Q (p.Arg34Gln), TOPMed rs941101723, gnomAD rs941101723, REVEL 0.07, CADD 0.07
- R34W (p.Arg34Trp), 1000Genomes rs201934979, ESP rs201934979, TOPMed rs201934979, gnomAD rs201934979, REVEL 0.07, CADD 15.80
- R34R (p.Arg34Arg), gnomAD 15-74749840-G-A, CADD 6.13
- V35G (p.Val35Gly), gnomAD rs1192297220, REVEL 0.26, CADD 22.20
- V35S (p.Val35Ser), rs758752876, gnomAD 15-74749838-CG-C, CADD 2.84
- V35A (p.Val35Ala), gnomAD 15-74749842-T-C, REVEL 0.15, CADD 21.80
- V35V (p.Val35Val), gnomAD 15-74749843-C-G, CADD 4.39
- P36L (p.Pro36Leu), gnomAD rs1174406258, REVEL 0.44, CADD 23.50
- P36S (p.Pro36Ser), ESP rs146974121, ExAC rs146974121, TOPMed rs146974121, gnomAD rs146974121, REVEL 0.45, CADD 24.40
- P36T (p.Pro36Thr), ESP rs146974121, ExAC rs146974121, TOPMed rs146974121, gnomAD rs146974121, REVEL 0.50, CADD 24.20
- K37* (p.Lys37Ter), TOPMed rs1313870798, CADD 34.00
- K37I (p.Lys37Ile), ExAC rs751602658, TOPMed rs751602658, gnomAD rs751602658, REVEL 0.31, CADD 25.10
- K37R (p.Lys37Arg), ExAC rs751602658, TOPMed rs751602658, gnomAD rs751602658, REVEL 0.05, CADD 20.70
- K37Q (p.Lys37Gln), gnomAD 15-74749842-T-TC, CADD 23.30
- G38P (p.Gly38Pro), gnomAD 15-74749849-AGG-A, CADD 27.90
- G38D (p.Gly38Asp), gnomAD 15-74749851-G-A, REVEL 0.59, CADD 24.20
- G38G (p.Gly38Gly), rs762047920, gnomAD 15-74749852-C-T, CADD 9.80
- L39M (p.Leu39Met), gnomAD 15-74749853-C-A, REVEL 0.17, CADD 22.70
- L39P (p.Leu39Pro), gnomAD 15-74749854-T-C, REVEL 0.39, CADD 25.20
- L39L (p.Leu39Leu), rs767672496, gnomAD 15-74749855-G-A, CADD 7.92
- K40R (p.Lys40Arg), ExAC rs200789139, TOPMed rs200789139, gnomAD rs200789139, REVEL 0.16, CADD 22.50
- p.Lys40 Trp46delinsArg, gnomAD 15-74749856-AAAAG, CADD 19.00
- S41G (p.Ser41Gly), TOPMed rs2063305378
- P42L (p.Pro42Leu), Ensembl rs72547511
- P42R (p.Pro42Arg), rs72547511, UniProt VAR 025182, Ensembl rs72547511, AlphaMissense 0.44, MetaLR 0.77, Benign, in allele CYP1A2*15
- P42S (p.Pro42Ser), ExAC rs756500317, gnomAD rs756500317, REVEL 0.38, CADD 23.80
- P42P (p.Pro42Pro), rs1303772001, gnomAD 15-74749864-A-G, CADD 1.13
- P43L (p.Pro43Leu), gnomAD 15-74749866-C-T, REVEL 0.89, CADD 24.40
- E44K (p.Glu44Lys), ExAC rs3743482, gnomAD rs3743482, REVEL 0.41, CADD 24.10
- E44G (p.Glu44Gly), gnomAD 15-74749869-A-G, REVEL 0.13, CADD 15.90
- P45L (p.Pro45Leu), gnomAD 15-74749872-C-T, REVEL 0.92, CADD 25.20
- P45P (p.Pro45Pro), gnomAD 15-74749873-A-G, CADD 8.30
- W46* (p.Trp46Ter), 1000Genomes rs568839929, ExAC rs568839929, gnomAD rs568839929, CADD 35.00
- W46C (p.Trp46Cys), 1000Genomes rs539368728, ExAC rs539368728, TOPMed rs539368728, gnomAD rs539368728
- G47C (p.Gly47Cys), gnomAD rs939000746, REVEL 0.32, CADD 21.10
- G47D (p.Gly47Asp), ExAC rs777457540, gnomAD rs777457540, REVEL 0.33, CADD 22.80
- G47S (p.Gly47Ser), gnomAD rs939000746, REVEL 0.08, CADD 14.40
- G47V (p.Gly47Val), ExAC rs777457540, gnomAD rs777457540, REVEL 0.43, CADD 24.20
- G47G (p.Gly47Gly), gnomAD 15-74749879-C-A, CADD 5.48
- W48* (p.Trp48Ter), gnomAD rs1215275194, CADD 35.00
- W48G (p.Trp48Gly), rs201763966, ClinGen CA7659695, ClinVar RCV004194780, 1000Genomes rs201763966, REVEL 0.40, CADD 25.90, Uncertain significance, not specified
- W48L (p.Trp48Leu), TOPMed rs2063305551
- W48C (p.Trp48Cys), gnomAD 15-74749882-G-C, REVEL 0.53, CADD 25.60
- P49A (p.Pro49Ala), gnomAD rs946281188, REVEL 0.72, CADD 24.00
- P49T (p.Pro49Thr), gnomAD rs946281188
- P49P (p.Pro49Pro), rs780893195, gnomAD 15-74749885-C-T, CADD 5.20
- L50F (p.Leu50Phe), TOPMed rs1393868624, gnomAD rs1393868624, REVEL 0.08, CADD 12.10
- L50L (p.Leu50Leu), rs1393868624, gnomAD 15-74749888-G-A, CADD 5.18
- L51F (p.Leu51Phe), ExAC rs745706596, TOPMed rs745706596, gnomAD rs745706596, REVEL 0.18, CADD 12.00
- L51V (p.Leu51Val), NCI-TCGA Cosmic COSV5966, Variant assessed as somatic; moderate impact.
- L51L (p.Leu51Leu), rs147610197, gnomAD 15-74749891-C-T, CADD 0.29
- G52R (p.Gly52Arg), ESP rs376605220, ExAC rs376605220, TOPMed rs376605220, gnomAD rs376605220, REVEL 0.93, CADD 24.40
- G52E (p.Gly52Glu), gnomAD 15-74749893-G-A, REVEL 0.88, CADD 25.40
- H53L (p.His53Leu), ExAC rs762906326, TOPMed rs762906326, gnomAD rs762906326, REVEL 0.41, CADD 25.00
- H53N (p.His53Asn), TOPMed rs1420021422, gnomAD rs1420021422, REVEL 0.12, CADD 10.50
- H53Y (p.His53Tyr), TOPMed rs1420021422, gnomAD rs1420021422
- H53R (p.His53Arg), gnomAD 15-74749896-A-G, REVEL 0.47, CADD 24.40
- H53H (p.His53His), gnomAD 15-74749897-T-C, CADD 2.83
- V54V (p.Val54Val), gnomAD 15-74749900-G-A, CADD 9.00
- L55L (p.Leu55Leu), gnomAD 15-74749901-C-T, CADD 9.03
- T56A (p.Thr56Ala), gnomAD rs1378709714, REVEL 0.10, CADD 22.80
- T56T (p.Thr56Thr), rs1567204937, gnomAD 15-74749906-C-T, CADD 8.17
- L57M (p.Leu57Met), gnomAD 15-74749907-C-A, REVEL 0.45, CADD 19.90
- L57L (p.Leu57Leu), rs768527903, gnomAD 15-74749907-C-T, CADD 7.22
- G58E (p.Gly58Glu), NCI-TCGA Cosmic COSV5966, Variant assessed as somatic; moderate impact.
- K59R (p.Lys59Arg), TOPMed rs1177351603, gnomAD rs1177351603, REVEL 0.13, CADD 20.00
- K59Q (p.Lys59Gln), gnomAD 15-74749913-A-C, REVEL 0.24, CADD 23.00
- N60K (p.Asn60Lys), gnomAD 15-74749918-C-G, REVEL 0.32, CADD 20.40
- N60N (p.Asn60Asn), rs774423284, gnomAD 15-74749918-C-T, CADD 7.79
- P61L (p.Pro61Leu), ExAC rs761818825, TOPMed rs761818825, gnomAD rs761818825, REVEL 0.50, CADD 24.80
- P61S (p.Pro61Ser), Ensembl rs760561182, REVEL 0.61, CADD 23.90
- P61P (p.Pro61Pro), rs998822071, gnomAD 15-74749921-G-A, CADD 0.79
- H62Y (p.His62Tyr), gnomAD 15-74749922-C-T, REVEL 0.53, CADD 22.40
- H62Q (p.His62Gln), gnomAD 15-74749924-C-A, REVEL 0.63, CADD 22.10
- H62H (p.His62His), rs1291681307, gnomAD 15-74749924-C-T, CADD 5.67
- L63L (p.Leu63Leu), rs1180170785, gnomAD 15-74749925-C-T, CADD 6.83
- L63P (p.Leu63Pro), gnomAD 15-74749926-T-C, REVEL 0.63, CADD 26.40
- A64T (p.Ala64Thr), ExAC rs753312654, TOPMed rs753312654, gnomAD rs753312654, REVEL 0.10, CADD 14.40
- A64P (p.Ala64Pro), gnomAD 15-74749928-G-C, REVEL 0.43, CADD 23.70
- A64A (p.Ala64Ala), rs1237099155, gnomAD 15-74749930-A-C, CADD 0.38
- L65P (p.Leu65Pro), ESP rs71651689, ExAC rs71651689, TOPMed rs71651689, gnomAD rs71651689, REVEL 0.90, CADD 25.10
- L65M (p.Leu65Met), gnomAD 15-74749931-C-A, REVEL 0.54, CADD 23.00
- S66T (p.Ser66Thr), gnomAD 15-74749934-T-A, REVEL 0.14, CADD 0.01
- S66* (p.Ser66Ter), gnomAD 15-74749935-C-G, CADD 33.00
- S66S (p.Ser66Ser), rs2063305843, gnomAD 15-74749936-A-C, CADD 0.17
- R67G (p.Arg67Gly), ExAC rs760996321, gnomAD rs760996321, REVEL 0.32, CADD 4.16
- R67R (p.Arg67Arg), rs760996321, gnomAD 15-74749937-A-C, CADD 1.31
- R67K (p.Arg67Lys), gnomAD 15-74749938-G-A, REVEL 0.17, CADD 0.00
- R67S (p.Arg67Ser), gnomAD 15-74749939-G-C, REVEL 0.24, CADD 14.70
- M68I (p.Met68Ile), rs2505554714, ClinGen CA393177599, ClinVar RCV004161958, Uncertain significance, not specified
Public CYP1A2 analysis runs
- CYP1A2 analysis run — CYP1A2 (1,023 variants) — completed 2026-08-18