ALDH2 (P05091) variants and mutations
ALDH2 (also known as P05091) is a human protein-coding gene encoding an aldehyde dehydrogenase, mitochondrial protein. It clears acetaldehyde and other reactive aldehydes within mitochondria, limiting toxic aldehyde accumulation after alcohol exposure and oxidative stress. The common ALDH2*2 allele sharply reduces activity, causing alcohol flushing and modifying alcohol-related disease risk. This analysis covers 761 ALDH2 variants and mutations. Of these, 83% have computational variant effect predictions. Disease context includes alcohol dependence, alcohol drinking, and AMED syndrome, digenic. Example ALDH2 variants include L2M, L2L, and L2F.
Variant analysis overview
- Gene: ALDH2
- Protein: P05091
- UniProt accession: P05091
- Organism: Homo sapiens
- Variants analyzed: 761
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 570 unspecified-consequence records; 110 missense variants; 61 synonymous variants; 8 frameshift variants; 2 in-frame deletions; 7 stop-gained variants; 1 in-frame insertions; 2 splice-region variants
- Prediction scores: 628 variants have prediction scores (83% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: alcohol dependence, alcohol drinking, AMED syndrome, digenic, gout, coronary artery disorder, parasitic infectious disease, type 2 diabetes mellitus, atrial fibrillation, ischemic stroke, cirrhosis of liver, chronic obstructive pulmonary disease, alcohol-related disorders.
Protein structure and variant hotspots
- Protein features: 1 binding sites; 9 post-translational modification sites.
- PTM context: 9 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 ALDH2 variants
Examples include L2M, L2L, L2F, R3C, R3P, R3S, R3G, R3H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- L2M (p.Leu2Met), gnomAD 12-111766986-T-A, REVEL 0.28, CADD 14.00
- L2L (p.Leu2Leu), rs777511085, gnomAD 12-111766986-T-C, CADD 7.21
- L2F (p.Leu2Phe), gnomAD 12-111766988-G-T, REVEL 0.34, CADD 22.70
- R3C (p.Arg3Cys), TOPMed rs1373907435, gnomAD rs1373907435, REVEL 0.25, CADD 24.20
- R3P (p.Arg3Pro), TOPMed rs1862055824, gnomAD rs1862055824, REVEL 0.24, CADD 23.70
- R3S (p.Arg3Ser), TOPMed rs1373907435, gnomAD rs1373907435, REVEL 0.19, CADD 23.20
- R3G (p.Arg3Gly), gnomAD 12-111766989-C-G, REVEL 0.19, CADD 23.50
- R3H (p.Arg3His), gnomAD 12-111766990-G-A, REVEL 0.26, CADD 22.50
- R3R (p.Arg3Arg), rs6490301, gnomAD 12-111766991-C-T, CADD 9.19
- A4S (p.Ala4Ser), TOPMed rs2068162511, REVEL 0.15, CADD 16.60
- A4T (p.Ala4Thr), TOPMed rs2068162511, REVEL 0.13, CADD 18.20
- A4V (p.Ala4Val), TOPMed rs893145442, REVEL 0.13, CADD 16.00
- A4P (p.Ala4Pro), gnomAD 12-111766992-G-C, REVEL 0.21, CADD 20.10
- A4D (p.Ala4Asp), gnomAD 12-111766993-C-A, REVEL 0.22, CADD 17.10
- A4A (p.Ala4Ala), gnomAD 12-111766994-T-C, CADD 9.21
- A5T (p.Ala5Thr), 1000Genomes rs551088152, TOPMed rs551088152, gnomAD rs551088152, REVEL 0.14, CADD 17.00
- A5S (p.Ala5Ser), gnomAD 12-111766995-G-T, REVEL 0.16, CADD 15.80
- A5P (p.Ala5Pro), gnomAD 12-111766995-G-C, REVEL 0.26, CADD 18.90
- A5V (p.Ala5Val), gnomAD 12-111766996-C-T, REVEL 0.13, CADD 16.70
- A5A (p.Ala5Ala), rs2068162629, gnomAD 12-111766997-C-T, CADD 7.90
- A6P (p.Ala6Pro), TOPMed rs1336401827, gnomAD rs1336401827, REVEL 0.22, CADD 9.71
- A6S (p.Ala6Ser), TOPMed rs1336401827, gnomAD rs1336401827, REVEL 0.10, CADD 2.08
- A6V (p.Ala6Val), gnomAD rs1213920796, REVEL 0.10, CADD 13.50
- A6R (p.Ala6Arg), gnomAD 12-111766996-CCGC, CADD 21.70
- A6T (p.Ala6Thr), gnomAD 12-111766998-G-A, REVEL 0.14, CADD 6.81
- A6A (p.Ala6Ala), rs1271914644, gnomAD 12-111767000-C-A, CADD 9.13
- R7C (p.Arg7Cys), ExAC rs766577822, TOPMed rs766577822, gnomAD rs766577822, REVEL 0.23, CADD 15.90
- R7G (p.Arg7Gly), ExAC rs766577822, TOPMed rs766577822, gnomAD rs766577822, REVEL 0.11, CADD 7.10
- R7H (p.Arg7His), 1000Genomes rs566590864, ExAC rs566590864, TOPMed rs566590864, gnomAD rs566590864, REVEL 0.28, CADD 14.50
- R7L (p.Arg7Leu), cosmic curated COSV55665, 1000Genomes rs566590864, ExAC rs566590864, TOPMed rs566590864, REVEL 0.17, CADD 12.60
- R7A (p.Arg7Ala), gnomAD 12-111766998-GC-G, CADD 21.00
- R7S (p.Arg7Ser), gnomAD 12-111767001-C-A, REVEL 0.09, CADD 3.92
- R7P (p.Arg7Pro), gnomAD 12-111767002-G-C, REVEL 0.19, CADD 13.70
- R7R (p.Arg7Arg), gnomAD 12-111767003-C-T, CADD 11.20
- F8L (p.Phe8Leu), TOPMed rs1210605825, gnomAD rs1210605825, REVEL 0.09, CADD 9.20
- F8F (p.Phe8Phe), rs1210605825, gnomAD 12-111767006-C-T, CADD 9.58
- G9R (p.Gly9Arg), TOPMed rs1311306580, gnomAD rs1311306580, REVEL 0.17, CADD 11.90, Uncertain significance, not specified
- G9W (p.Gly9Trp), gnomAD 12-111767007-G-T, REVEL 0.31, CADD 16.10
- G9V (p.Gly9Val), gnomAD 12-111767008-G-T, REVEL 0.17, CADD 14.00
- G9E (p.Gly9Glu), gnomAD 12-111767008-G-A, REVEL 0.15, CADD 14.70
- G9G (p.Gly9Gly), gnomAD 12-111767009-G-A, CADD 8.82
- P10R (p.Pro10Arg), TOPMed rs1286567155, gnomAD rs1286567155, REVEL 0.26, CADD 12.30
- P10S (p.Pro10Ser), gnomAD 12-111767010-C-T, REVEL 0.12, CADD 12.20
- P10T (p.Pro10Thr), gnomAD 12-111767010-C-A, REVEL 0.15, CADD 12.00
- P10H (p.Pro10His), gnomAD 12-111767011-C-A, REVEL 0.25, CADD 12.90
- P10L (p.Pro10Leu), gnomAD 12-111767011-C-T, REVEL 0.21, CADD 12.80
- P10P (p.Pro10Pro), rs2068163002, gnomAD 12-111767012-C-T, CADD 9.18
- R11L (p.Arg11Leu), TOPMed rs2068163053, gnomAD rs2068163053, REVEL 0.10, CADD 14.30
- R11S (p.Arg11Ser), Ensembl rs2136003986, REVEL 0.10, CADD 8.51
- R11A (p.Arg11Ala), gnomAD 12-111767009-GC-G, CADD 21.00
- R11C (p.Arg11Cys), gnomAD 12-111767013-C-T, REVEL 0.26, CADD 19.20
- R11H (p.Arg11His), gnomAD 12-111767014-G-A, REVEL 0.21, CADD 15.00
- R11R (p.Arg11Arg), gnomAD 12-111767015-C-A, CADD 6.82
- L12P (p.Leu12Pro), TOPMed rs1215850690, gnomAD rs1215850690, REVEL 0.26, CADD 19.20
- L12M (p.Leu12Met), gnomAD 12-111767016-C-A, REVEL 0.19, CADD 16.30
- L12Q (p.Leu12Gln), gnomAD 12-111767017-T-A, REVEL 0.17, CADD 18.60
- L12L (p.Leu12Leu), gnomAD 12-111767018-G-C, CADD 9.90
- G13D (p.Gly13Asp), NCI-TCGA TCGA novel, REVEL 0.12, CADD 19.40, Variant assessed as somatic; moderate impact.
- G13A (p.Gly13Ala), gnomAD 12-111767017-TG-T, CADD 23.60
- G13S (p.Gly13Ser), gnomAD 12-111767019-G-A, REVEL 0.09, CADD 15.40
- G13C (p.Gly13Cys), gnomAD 12-111767019-G-T, REVEL 0.15, CADD 21.10
- G13V (p.Gly13Val), gnomAD 12-111767020-G-T, REVEL 0.13, CADD 18.30
- G13G (p.Gly13Gly), rs1064903, gnomAD 12-111767021-C-T, CADD 11.30
- R14G (p.Arg14Gly), gnomAD rs2068163225, REVEL 0.26, CADD 17.20
- R14L (p.Arg14Leu), TOPMed rs2068163257, REVEL 0.27, CADD 16.30
- R14P (p.Arg14Pro), gnomAD 12-111767006-C-CG, CADD 20.80
- R14A (p.Arg14Ala), gnomAD 12-111767020-GC-G, CADD 22.80
- R14C (p.Arg14Cys), gnomAD 12-111767022-C-T, REVEL 0.28, CADD 22.50
- R14S (p.Arg14Ser), gnomAD 12-111767022-C-A, REVEL 0.24, CADD 16.80
- R14H (p.Arg14His), gnomAD 12-111767023-G-A, REVEL 0.27, CADD 16.00
- R14R (p.Arg14Arg), gnomAD 12-111767024-C-T, CADD 12.30
- R15del (p.Arg15del), rs764941692, gnomAD 12-111767019-GGCC, CADD 16.70
- R15C (p.Arg15Cys), gnomAD 12-111767025-C-T, REVEL 0.27, CADD 22.80
- R15S (p.Arg15Ser), gnomAD 12-111767025-C-A, REVEL 0.20, CADD 18.90
- R15H (p.Arg15His), gnomAD 12-111767026-G-A, REVEL 0.28, CADD 21.70
- R15L (p.Arg15Leu), gnomAD 12-111767026-G-T, REVEL 0.24, CADD 20.80
- R15R (p.Arg15Arg), gnomAD 12-111767027-C-A, CADD 8.42
- L16F (p.Leu16Phe), ExAC rs755268259, TOPMed rs755268259, gnomAD rs755268259, REVEL 0.10, CADD 3.20
- L16R (p.Leu16Arg), gnomAD rs916384497, REVEL 0.14, CADD 15.10, Uncertain significance, not specified
- L16H (p.Leu16His), gnomAD 12-111767019-GGCC, CADD 25.00
- L16I (p.Leu16Ile), gnomAD 12-111767028-C-A, REVEL 0.05, CADD 5.03
- L16P (p.Leu16Pro), gnomAD 12-111767029-T-C, REVEL 0.14, CADD 16.60
- L16L (p.Leu16Leu), gnomAD 12-111767030-C-G, CADD 4.41
- L17W (p.Leu17Trp), 1000Genomes rs372948453, TOPMed rs372948453, gnomAD rs372948453, REVEL 0.36, CADD 19.30
- L17L (p.Leu17Leu), gnomAD 12-111767031-T-C, CADD 7.42
- L17M (p.Leu17Met), gnomAD 12-111767031-T-A, REVEL 0.22, CADD 5.75
- L17F (p.Leu17Phe), gnomAD 12-111767033-G-C, REVEL 0.24, CADD 9.92
- S18A (p.Ser18Ala), Ensembl rs2068163516
- S18P (p.Ser18Pro), gnomAD 12-111767034-T-C, REVEL 0.22, CADD 17.10
- S18T (p.Ser18Thr), gnomAD 12-111767034-T-A, REVEL 0.12, CADD 14.50
- S18L (p.Ser18Leu), gnomAD 12-111767035-C-T, REVEL 0.19, CADD 17.70
- S18* (p.Ser18Ter), gnomAD 12-111767035-C-G, CADD 33.00
- S18S (p.Ser18Ser), gnomAD 12-111767036-A-G, CADD 3.32
- A19P (p.Ala19Pro), gnomAD rs1441105785, REVEL 0.22, CADD 15.60
- A19S (p.Ala19Ser), gnomAD rs1441105785, REVEL 0.12, CADD 11.10
- A19T (p.Ala19Thr), gnomAD 12-111767037-G-A, REVEL 0.11, CADD 14.70
- A19V (p.Ala19Val), gnomAD 12-111767038-C-T, REVEL 0.10, CADD 12.00
- A19D (p.Ala19Asp), gnomAD 12-111767038-C-A, REVEL 0.15, CADD 13.00
- A19A (p.Ala19Ala), rs1164016538, gnomAD 12-111767039-C-T, CADD 8.30
- A20T (p.Ala20Thr), TOPMed rs1002692747, REVEL 0.21, CADD 15.60
- A20S (p.Ala20Ser), gnomAD 12-111767040-G-T, REVEL 0.23, CADD 12.70
- A20V (p.Ala20Val), gnomAD 12-111767041-C-T, REVEL 0.18, CADD 13.60
- A20D (p.Ala20Asp), gnomAD 12-111767041-C-A, REVEL 0.26, CADD 17.40
- A20A (p.Ala20Ala), gnomAD 12-111767042-C-A, CADD 6.74
- A21T (p.Ala21Thr), gnomAD rs1395989016, REVEL 0.17, CADD 13.80
- p.Ala21dup, gnomAD 12-111767036-A-AG, CADD 12.50
- A21del (p.Ala21del), rs1476255866, gnomAD 12-111767036-AGCC, CADD 12.40
- A21S (p.Ala21Ser), gnomAD 12-111767043-G-T, REVEL 0.18, CADD 8.45
- A21P (p.Ala21Pro), gnomAD 12-111767043-G-C, REVEL 0.28, CADD 18.40
- A21V (p.Ala21Val), gnomAD 12-111767044-C-T, REVEL 0.25, CADD 15.50
- A21D (p.Ala21Asp), gnomAD 12-111767044-C-A, REVEL 0.31, CADD 19.10
- A21A (p.Ala21Ala), gnomAD 12-111767045-C-A, CADD 9.07
- T22S (p.Thr22Ser), gnomAD 12-111767046-A-T, REVEL 0.09, CADD 5.35
- T22A (p.Thr22Ala), gnomAD 12-111767046-A-G, REVEL 0.09, CADD 2.10
- T22I (p.Thr22Ile), gnomAD 12-111767047-C-T, REVEL 0.13, CADD 13.60
- T22N (p.Thr22Asn), gnomAD 12-111767047-C-A, REVEL 0.12, CADD 12.30
- T22T (p.Thr22Thr), rs781131621, gnomAD 12-111767048-C-A, CADD 9.14
- Q23R (p.Gln23Arg), TOPMed rs1330573776, gnomAD rs1330573776, REVEL 0.10, CADD 13.00
- Q23* (p.Gln23Ter), gnomAD 12-111767049-C-T, CADD 33.00
- Q23E (p.Gln23Glu), gnomAD 12-111767049-C-G, REVEL 0.07, CADD 7.46
- Q23K (p.Gln23Lys), gnomAD 12-111767049-C-A, REVEL 0.05, CADD 10.50
- Q23P (p.Gln23Pro), gnomAD 12-111767050-A-C, REVEL 0.13, CADD 13.20
- Q23Q (p.Gln23Gln), rs1354902575, gnomAD 12-111767051-G-A, CADD 7.65
- Q23H (p.Gln23His), gnomAD 12-111767051-G-T, REVEL 0.19, CADD 12.70
- A24V (p.Ala24Val), TOPMed rs1414093989, gnomAD rs1414093989, REVEL 0.11, CADD 17.30
- A24T (p.Ala24Thr), gnomAD 12-111767052-G-A, REVEL 0.17, CADD 17.60
- A24S (p.Ala24Ser), gnomAD 12-111767052-G-T, REVEL 0.15, CADD 16.40
- A24D (p.Ala24Asp), gnomAD 12-111767053-C-A, REVEL 0.19, CADD 13.90
- A24A (p.Ala24Ala), rs200369180, gnomAD 12-111767054-C-T, CADD 4.02
- V25A (p.Val25Ala), 1000Genomes rs2136004046, REVEL 0.25, CADD 21.60
- V25M (p.Val25Met), TOPMed rs2068163983, REVEL 0.21, CADD 18.00
- V25L (p.Val25Leu), gnomAD 12-111767055-G-T, REVEL 0.21, CADD 13.80
- V25V (p.Val25Val), gnomAD 12-111767057-G-T, CADD 9.36
- P26T (p.Pro26Thr), Ensembl rs866937515, REVEL 0.26, CADD 22.30
- P26S (p.Pro26Ser), gnomAD 12-111767058-C-T, REVEL 0.26, CADD 22.60
- P26L (p.Pro26Leu), gnomAD 12-111767059-C-T, REVEL 0.33, CADD 22.80
- P26H (p.Pro26His), gnomAD 12-111767059-C-A, REVEL 0.42, CADD 23.80
- P26P (p.Pro26Pro), gnomAD 12-111767060-T-C, CADD 9.50
- A27S (p.Ala27Ser), TOPMed rs1356795930, gnomAD rs1356795930, REVEL 0.14, CADD 8.72
- A27T (p.Ala27Thr), TOPMed rs1356795930, gnomAD rs1356795930, REVEL 0.18, CADD 13.00
- A27V (p.Ala27Val), gnomAD rs1233413221, REVEL 0.18, CADD 19.30
- A27P (p.Ala27Pro), gnomAD 12-111767061-G-C, REVEL 0.18, CADD 14.10
- A27D (p.Ala27Asp), gnomAD 12-111767062-C-A, REVEL 0.21, CADD 19.40
- A27A (p.Ala27Ala), gnomAD 12-111767063-C-A, CADD 11.20
- P28L (p.Pro28Leu), gnomAD rs1269099351, REVEL 0.43, CADD 24.50
- P28R (p.Pro28Arg), gnomAD rs1269099351, REVEL 0.42, CADD 24.40
- P28S (p.Pro28Ser), gnomAD 12-111767064-C-T, REVEL 0.34, CADD 22.70
- P28T (p.Pro28Thr), gnomAD 12-111767064-C-A, REVEL 0.36, CADD 23.70
- P28A (p.Pro28Ala), gnomAD 12-111767064-C-G, REVEL 0.32, CADD 22.10
- P28H (p.Pro28His), gnomAD 12-111767065-C-A, REVEL 0.43, CADD 24.60
- P28P (p.Pro28Pro), rs2068164283, gnomAD 12-111767066-C-T, CADD 12.20
- N29D (p.Asn29Asp), Ensembl rs923676854, REVEL 0.26, CADD 16.80
- N29H (p.Asn29His), Ensembl rs923676854
- N29S (p.Asn29Ser), ExAC rs756057023, TOPMed rs756057023, gnomAD rs756057023, REVEL 0.26, CADD 14.50
- N29T (p.Asn29Thr), gnomAD 12-111767061-GC-G, CADD 24.20
- N29K (p.Asn29Lys), gnomAD 12-111767069-C-A, REVEL 0.20, CADD 10.30
- N29N (p.Asn29Asn), gnomAD 12-111767069-C-T, CADD 9.81
- Q30* (p.Gln30Ter), TOPMed rs1035974154, gnomAD rs1035974154, CADD 35.00
- Q30E (p.Gln30Glu), cosmic curated COSV10506, TOPMed rs1035974154, gnomAD rs1035974154, REVEL 0.05, CADD 15.20
- Q30H (p.Gln30His), rs2542330746, ClinGen CA386739010, ClinVar RCV004287118, REVEL 0.04, CADD 20.40, Uncertain significance, not specified
- Q30K (p.Gln30Lys), gnomAD 12-111767070-C-A, REVEL 0.05, CADD 16.10
- Q30R (p.Gln30Arg), gnomAD 12-111767071-A-G, REVEL 0.03, CADD 16.00
- Q30L (p.Gln30Leu), gnomAD 12-111767071-A-T, REVEL 0.07, CADD 18.10
- Q30Q (p.Gln30Gln), gnomAD 12-111767072-G-A, CADD 12.80
- Q31H (p.Gln31His), TOPMed rs1187692647, gnomAD rs1187692647, REVEL 0.05, CADD 21.30
- Q31R (p.Gln31Arg), TOPMed rs1275543545, gnomAD rs1275543545, REVEL 0.05, CADD 22.30
- Q31K (p.Gln31Lys), gnomAD 12-111767073-C-A, REVEL 0.06, CADD 17.90
- Q31* (p.Gln31Ter), gnomAD 12-111767073-C-T, CADD 35.00
- Q31Q (p.Gln31Gln), gnomAD 12-111767075-G-A, CADD 12.90
- P32T (p.Pro32Thr), gnomAD 12-111767076-C-A, REVEL 0.11, CADD 23.10
- P32A (p.Pro32Ala), gnomAD 12-111767076-C-G, REVEL 0.08, CADD 20.20
- P32S (p.Pro32Ser), gnomAD 12-111767076-C-T, REVEL 0.09, CADD 23.00
- P32L (p.Pro32Leu), gnomAD 12-111767077-C-T, REVEL 0.17, CADD 22.60
- P32H (p.Pro32His), gnomAD 12-111767077-C-A, REVEL 0.14, CADD 25.80
- P32P (p.Pro32Pro), gnomAD 12-111767078-C-A, CADD 10.10
- E33D (p.Glu33Asp), gnomAD rs1256069672, REVEL 0.03, CADD 15.50
- E33K (p.Glu33Lys), gnomAD rs1483619171, REVEL 0.08, CADD 22.40
- E33V (p.Glu33Val), TOPMed rs1210769557, gnomAD rs1210769557, REVEL 0.10, CADD 24.40
- E33* (p.Glu33Ter), gnomAD 12-111767079-G-T, CADD 36.00
- E33G (p.Glu33Gly), gnomAD 12-111767080-A-G, REVEL 0.08, CADD 24.80
Public ALDH2 analysis runs
- ALDH2 analysis run — ALDH2 (761 variants) — completed 2026-08-18