AR (Androgen receptor) variants and mutations
AR (also known as Androgen receptor) is a human protein-coding gene encoding an androgen receptor protein. Androgen binding redirects its transcriptional program to control male sexual differentiation, reproductive physiology, muscle and bone biology, and other androgen-responsive processes. Loss-of-function variants cause androgen insensitivity, CAG expansion causes spinal and bulbar muscular atrophy, and persistent signaling drives prostate cancer. This analysis covers 4,045 AR variants and mutations. Of these, 22% have computational variant effect predictions. Disease context includes cancer, neurodegenerative disease, and Precordial pain. Example AR variants include M1L, E2D, and E2G.
Variant analysis overview
- Gene: AR
- Protein: Androgen receptor
- UniProt accession: P10275
- Organism: Homo sapiens
- Variants analyzed: 4045
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 3,853 unspecified-consequence records; 2 natural variant; 3 stop lost; 10 frameshift variants; 1 stop retained variant; 66 synonymous variants; 87 missense variants; 5 in-frame deletions; 2 splice-region variants; 4 stop-gained variants; 11 substitution
- Prediction scores: 899 variants have prediction scores (22% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: cancer, neurodegenerative disease, Precordial pain, colorectal adenocarcinoma, hair color, breast fibrocystic disease, rheumatic heart disease, breast carcinoma, neoplasm, jaw disease, colorectal carcinoma, breast cancer.
Protein structure and variant hotspots
- Protein features: 1 domains; 3 binding sites; 15 post-translational modification sites.
- Structural context: 979 variants have structural context.
- PTM context: 73 variants overlap post-translational modification sites.
- Experimental data: 60 protein positions have experimental scores. Source: AR Zinc finger, nuclear hormone receptor-type domain domainome 1.0.
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, ClinGen, MaveDB, LitVar.
Notable AR variants
Examples include M1L, E2D, E2G, E2K, E2Q, V3E, V3G, V3L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs2147313671, ClinGen CA413423582, ClinVar RCV001964227, MetaLR 0.82, MetaSVM 0.78, Pathogenic, Androgen resistance syndrome; Kennedy disease; Differences in sex development
- E2D (p.Glu2Asp), ESP rs377416804, TOPMed rs377416804
- E2G (p.Glu2Gly), rs1929637005, ClinGen CA413423592, ClinVar RCV001056718, Ensembl rs1929637005, AlphaMissense 0.89, MetaLR 0.82, Uncertain significance, in PAIS
- E2K (p.Glu2Lys), rs104894742, ClinGen CA120767, ClinVar RCV000010515, UniProt VAR 004679, CADD 12.20, Pathogenic, in PAIS
- E2Q (p.Glu2Gln), Ensembl rs104894742, Pathogenic, in PAIS
- V3E (p.Val3Glu), Ensembl rs2147313692
- V3G (p.Val3Gly), Ensembl rs2147313692
- V3L (p.Val3Leu), ExAC rs778912582, TOPMed rs778912582, gnomAD rs778912582, Likely pathogenic
- V3M (p.Val3Met), rs778912582, ClinGen CA10436200, ClinVar RCV001988640, ClinVar RCV002492261, AlphaMissense 0.83, MetaLR 0.83, Conflicting interpretations, Kennedy disease; Hypospadias 1, X-linked; Partial androgen insensitivity syndrom
- Q4A (p.Gln4Ala), cosmic curated COSV10531
- Q4* (p.Gln4Ter), Ensembl rs1929637461
- Q4E (p.Gln4Glu), Ensembl rs1929637461
- Q4L (p.Gln4Leu), Ensembl rs2147313701
- Q4R (p.Gln4Arg), Ensembl rs2147313701, MetaLR 0.10, MetaSVM -1.02
- Q4H (p.Gln4His), cosmic curated COSV10101
- L5H (p.Leu5His), cosmic curated COSV10530
- L5* (p.Leu5Ter), Ensembl rs2147313707
- L5F (p.Leu5Phe), Ensembl rs2147313710
- L5I (p.Leu5Ile), Ensembl rs2147313702
- L5V (p.Leu5Val), Ensembl rs2147313702, MetaLR 0.05, MetaSVM -0.99
- G6A (p.Gly6Ala), ExAC rs748374135, TOPMed rs748374135, gnomAD rs748374135
- G6R (p.Gly6Arg), Ensembl rs2147313713
- G6V (p.Gly6Val), ExAC rs748374135, TOPMed rs748374135, gnomAD rs748374135
- G6W (p.Gly6Trp), Ensembl rs2147313713
- L7M (p.Leu7Met), Ensembl rs2147313740
- L7P (p.Leu7Pro), Ensembl rs1602142878
- L7Q (p.Leu7Gln), Ensembl rs1602142878
- L7V (p.Leu7Val), Ensembl rs2147313740, MetaLR 0.04, MetaSVM -1.01
- G8* (p.Gly8Ter), Ensembl rs2147313762
- G8E (p.Gly8Glu), Ensembl rs1876971289
- G8R (p.Gly8Arg), cosmic curated COSV10531, Ensembl rs2147313762
- R9G (p.Arg9Gly), Ensembl rs2147313774
- R9M (p.Arg9Met), Ensembl rs2147313779
- R9S (p.Arg9Ser), TOPMed rs1445338990, gnomAD rs1445338990
- R9W (p.Arg9Trp), Ensembl rs2147313774, MetaLR 0.04, MetaSVM -1.06
- V10A (p.Val10Ala), gnomAD rs1415557685
- V10D (p.Val10Asp), gnomAD rs1415557685
- V10F (p.Val10Phe), Ensembl rs2147313787
- V10G (p.Val10Gly), cosmic curated COSV65953, gnomAD rs1415557685, Uncertain significance, Inborn genetic diseases
- V10L (p.Val10Leu), Ensembl rs2147313787
- Y11* (p.Tyr11Ter), Ensembl rs2147313807
- Y11F (p.Tyr11Phe), Ensembl rs2147313802
- Y11H (p.Tyr11His), Ensembl rs2147313799
- Y11N (p.Tyr11Asn), Ensembl rs2147313799, MetaLR 0.07, MetaSVM -1.09
- P12A (p.Pro12Ala), TOPMed rs1283306896, gnomAD rs1283306896
- P12H (p.Pro12His), ExAC rs772148792, TOPMed rs772148792, gnomAD rs772148792
- P12L (p.Pro12Leu), ExAC rs772148792, TOPMed rs772148792, gnomAD rs772148792
- P12S (p.Pro12Ser), cosmic curated COSV10748, TOPMed rs1283306896, gnomAD rs1283306896, MetaLR 0.06, MetaSVM -1.08
- R13G (p.Arg13Gly), NCI-TCGA Cosmic COSV1010, cosmic curated COSV10101, NCI-TCGA Cosmic COSV6596, Ensembl rs1335991486, Uncertain significance, Inborn genetic diseases
- R13L (p.Arg13Leu), TOPMed rs1929639711
- R13P (p.Arg13Pro), TOPMed rs1929639711
- R13Q (p.Arg13Gln), TOPMed rs1929639711
- R13W (p.Arg13Trp), cosmic curated COSV65961, Ensembl rs1335991486
- P14A (p.Pro14Ala), Ensembl rs2147313827
- P14L (p.Pro14Leu), Ensembl rs1929640066
- P14R (p.Pro14Arg), Ensembl rs1929640066
- P14S (p.Pro14Ser), Ensembl rs2147313827
- P14T (p.Pro14Thr), Ensembl rs2147313827, MetaLR 0.05, MetaSVM -1.00
- P15A (p.Pro15Ala), Ensembl rs2147313849, REVEL 0.04, CADD 13.50
- P15L (p.Pro15Leu), NCI-TCGA Cosmic COSV6595, cosmic curated COSV65957, Ensembl rs2147313854, REVEL 0.03, CADD 18.50, Variant assessed as somatic; moderate impact.
- P15Q (p.Pro15Gln), Ensembl rs2147313854
- P15T (p.Pro15Thr), Ensembl rs2147313849, REVEL 0.04, CADD 10.70
- S16A (p.Ser16Ala), Ensembl rs2147313864
- S16C (p.Ser16Cys), Ensembl rs2147313874
- S16P (p.Ser16Pro), Ensembl rs2147313864
- S16T (p.Ser16Thr), Ensembl rs2147313864
- S16Y (p.Ser16Tyr), Ensembl rs2147313874
- K17M (p.Lys17Met), Ensembl rs2147313882
- K17N (p.Lys17Asn), rs370971743, ClinGen CA10436207, NCI-TCGA Cosmic COSV6595, cosmic curated COSV65955, AlphaMissense 0.85, MetaLR 0.83, Likely benign, Kennedy disease; Androgen resistance syndrome
- K17R (p.Lys17Arg), Ensembl rs2147313882, MetaLR 0.02, MetaSVM -0.96
- T18A (p.Thr18Ala), cosmic curated COSV10531, Ensembl rs2147313895
- T18N (p.Thr18Asn), Ensembl rs2147313907
- T18P (p.Thr18Pro), Ensembl rs2147313895
- T18S (p.Thr18Ser), Ensembl rs2147313895, MetaLR 0.07, MetaSVM -1.04
- Y19* (p.Tyr19Ter), Ensembl rs2147313928
- Y19C (p.Tyr19Cys), NCI-TCGA TCGA novel, Ensembl rs2147313923, Variant assessed as somatic; moderate impact.
- Y19F (p.Tyr19Phe), Ensembl rs2147313923
- Y19H (p.Tyr19His), Ensembl rs2147313917
- Y19N (p.Tyr19Asn), Ensembl rs2147313917
- Y19S (p.Tyr19Ser), Ensembl rs2147313923, MetaLR 0.02, MetaSVM -1.01
- R20* (p.Arg20Ter), Ensembl rs2147313936
- R20G (p.Arg20Gly), Ensembl rs2147313936
- R20P (p.Arg20Pro), TOPMed rs1297947716, gnomAD rs1297947716
- R20Q (p.Arg20Gln), TOPMed rs1297947716, gnomAD rs1297947716, Uncertain significance, Inborn genetic diseases
- G21S (p.Gly21Ser), cosmic curated COSV10531, Ensembl rs2147313849, MetaLR 0.12, MetaSVM -1.06
- G21A (p.Gly21Ala), cosmic curated COSV10592
- G21E (p.Gly21Glu), cosmic curated COSV10748, Ensembl rs2147313954
- G21R (p.Gly21Arg), Ensembl rs2147313951
- G21V (p.Gly21Val), Ensembl rs2147313954
- A22D (p.Ala22Asp), Ensembl rs2147313975, REVEL 0.04, CADD 18.40
- A22G (p.Ala22Gly), Ensembl rs2147313975
- A22P (p.Ala22Pro), Ensembl rs2147313968
- A22T (p.Ala22Thr), cosmic curated COSV65964, Ensembl rs2147313968, REVEL 0.02, CADD 16.40
- A22V (p.Ala22Val), Ensembl rs2147313975, REVEL 0.03, CADD 14.50
- A22S (p.Ala22Ser), cosmic curated COSV10531, MetaLR 0.04, MetaSVM -1.02
- F23L (p.Phe23Leu), cosmic curated COSV65958, Ensembl rs2147313994, MetaLR 0.05, MetaSVM -1.00
- Q24* (p.Gln24Ter), Ensembl rs2147313998
- Q24E (p.Gln24Glu), Ensembl rs2147313998
- Q24H (p.Gln24His), ESP rs199644815, ExAC rs199644815, TOPMed rs199644815, gnomAD rs199644815
- Q24K (p.Gln24Lys), Ensembl rs2147313998
- Q24L (p.Gln24Leu), Ensembl rs2147314002
- N25H (p.Asn25His), Ensembl rs2147314020
- N25I (p.Asn25Ile), gnomAD rs1230878869
- N25K (p.Asn25Lys), Ensembl rs2147314034
- N25S (p.Asn25Ser), gnomAD rs1230878869
- N25T (p.Asn25Thr), gnomAD rs1230878869
- L26M (p.Leu26Met), NCI-TCGA Cosmic COSV6596, cosmic curated COSV65964, Variant assessed as somatic; moderate impact.
- L26Q (p.Leu26Gln), Ensembl rs2147314044
- L26V (p.Leu26Val), Ensembl rs2147314038
- F27I (p.Phe27Ile), TOPMed rs1257545761, gnomAD rs1257545761
- F27L (p.Phe27Leu), cosmic curated COSV10971, TOPMed rs1257545761, gnomAD rs1257545761
- F27V (p.Phe27Val), TOPMed rs1257545761, gnomAD rs1257545761, MetaLR 0.05, MetaSVM -1.07
- Q28* (p.Gln28Ter), Ensembl rs2147314062
- Q28E (p.Gln28Glu), Ensembl rs2147314062
- Q28H (p.Gln28His), NCI-TCGA Cosmic COSV6595, cosmic curated COSV65955, Ensembl rs2147314081, Variant assessed as somatic; moderate impact.
- Q28K (p.Gln28Lys), Ensembl rs2147314062
- Q28L (p.Gln28Leu), Ensembl rs2147314072
- Q28R (p.Gln28Arg), Ensembl rs2147314072, MetaLR 0.06, MetaSVM -1.04
- S29L (p.Ser29Leu), cosmic curated COSV65957
- S29C (p.Ser29Cys), Ensembl rs2147314089
- S29G (p.Ser29Gly), Ensembl rs2147314089
- S29I (p.Ser29Ile), Ensembl rs2147314096
- S29N (p.Ser29Asn), Ensembl rs2147314096
- S29R (p.Ser29Arg), ExAC rs530034797, Likely benign
- V30A (p.Val30Ala), Ensembl rs2147314112
- V30E (p.Val30Glu), Ensembl rs2147314112
- V30G (p.Val30Gly), Ensembl rs2147314112
- V30L (p.Val30Leu), cosmic curated COSV10654, ExAC rs761416673, Uncertain significance
- V30M (p.Val30Met), rs761416673, NCI-TCGA Cosmic COSV6595, cosmic curated COSV65952, ExAC rs761416673, AlphaMissense 0.81, MetaLR 0.88, Uncertain significance, not specified
- R31C (p.Arg31Cys), NCI-TCGA Cosmic COSV1010, cosmic curated COSV10101, Ensembl rs2147314125, Variant assessed as somatic; moderate impact.
- R31G (p.Arg31Gly), Ensembl rs2147314125
- R31H (p.Arg31His), NCI-TCGA Cosmic COSV6595, cosmic curated COSV65955, Ensembl rs2147314132, Variant assessed as somatic; moderate impact.
- R31P (p.Arg31Pro), Ensembl rs2147314132
- R31S (p.Arg31Ser), NCI-TCGA Cosmic COSV1010, cosmic curated COSV10101, Ensembl rs2147314125, MetaLR 0.05, MetaSVM -1.06, Variant assessed as somatic; moderate impact.
- E32A (p.Glu32Ala), Ensembl rs2147314161
- E32G (p.Glu32Gly), Ensembl rs2147314161
- E32K (p.Glu32Lys), NCI-TCGA Cosmic COSV6595, cosmic curated COSV65955, Ensembl rs2147314151, Variant assessed as somatic; moderate impact.
- E32Q (p.Glu32Gln), Ensembl rs2147314151
- E32V (p.Glu32Val), Ensembl rs2147314161, MetaLR 0.13, MetaSVM -0.97
- V33E (p.Val33Glu), Ensembl rs2147314180
- V33G (p.Val33Gly), Ensembl rs2147314180
- V33L (p.Val33Leu), Ensembl rs2147314176, MetaLR 0.02, MetaSVM -0.99
- V33M (p.Val33Met), cosmic curated COSV10748
- I34F (p.Ile34Phe), Ensembl rs2147314190
- I34L (p.Ile34Leu), Ensembl rs2147314190
- I34M (p.Ile34Met), TOPMed rs1027110412, gnomAD rs1027110412
- I34N (p.Ile34Asn), rs995307851, ClinGen CA330757105, ClinVar RCV002786915, TOPMed rs995307851, AlphaMissense 0.95, MetaLR 0.87, Uncertain significance, Inborn genetic diseases
- Q35* (p.Gln35Ter), Ensembl rs2147314202, CADD 34.00
- Q35E (p.Gln35Glu), cosmic curated COSV65955, Ensembl rs2147314202, REVEL 0.16, CADD 18.70
- Q35H (p.Gln35His), Ensembl rs2147314211
- Q35K (p.Gln35Lys), Ensembl rs2147314202
- Q35L (p.Gln35Leu), Ensembl rs2147314204
- Q35R (p.Gln35Arg), Ensembl rs2147314204
- N36S (p.Asn36Ser), cosmic curated COSV65964, MetaLR 0.14, MetaSVM -0.95
- N36D (p.Asn36Asp), Ensembl rs2147314220
- N36K (p.Asn36Lys), Ensembl rs2147314229
- N36T (p.Asn36Thr), Ensembl rs2147314221
- N36Y (p.Asn36Tyr), Ensembl rs2147314220
- P37F (p.Pro37Phe), cosmic curated COSV10468
- P37L (p.Pro37Leu), cosmic curated COSV10531, Ensembl rs2147314241, CADD 4.80
- P37Q (p.Pro37Gln), Ensembl rs2147314241
- P37R (p.Pro37Arg), Ensembl rs2147314241
- P37S (p.Pro37Ser), Ensembl rs2147314232, CADD 8.60
- P37T (p.Pro37Thr), Ensembl rs2147314232, CADD 8.15
- G38C (p.Gly38Cys), Ensembl rs2147314252
- G38D (p.Gly38Asp), ExAC rs750105188
- G38R (p.Gly38Arg), Ensembl rs2147314252, MetaLR 0.04, MetaSVM -1.08
- P39H (p.Pro39His), TOPMed rs1357821861
- P39L (p.Pro39Leu), TOPMed rs1357821861, REVEL 0.34, CADD 23.30
- P39R (p.Pro39Arg), TOPMed rs1357821861
- P39S (p.Pro39Ser), Ensembl rs2147314262, MetaLR 0.03, MetaSVM -0.95
- P39T (p.Pro39Thr), Ensembl rs2147314262, REVEL 0.29, CADD 22.70
- R40G (p.Arg40Gly), Ensembl rs2147314279
- R40K (p.Arg40Lys), rs147842041, ClinGen CA10436213, ClinVar RCV003808760, ESP rs147842041, AlphaMissense 0.25, MetaLR 0.86, Likely benign, Kennedy disease; Androgen resistance syndrome
- R40M (p.Arg40Met), ESP rs147842041, ExAC rs147842041, TOPMed rs147842041, gnomAD rs147842041, Likely benign
- R40S (p.Arg40Ser), gnomAD rs1187096665
- R40T (p.Arg40Thr), ESP rs147842041, ExAC rs147842041, TOPMed rs147842041, gnomAD rs147842041, Likely benign
- R40W (p.Arg40Trp), Ensembl rs2147314279
- H41D (p.His41Asp), TOPMed rs1229716168
- H41L (p.His41Leu), Ensembl rs2147314304
Public AR analysis runs
- AR analysis run — AR (4,045 variants) — completed 2026-08-18