ATXN2 (Ataxin-2) variants and mutations
ATXN2 (also known as Ataxin-2) is a human protein-coding gene encoding an ataxin-2 protein. It participates in RNA metabolism, stress-granule biology, and neuronal protein homeostasis. CAG-repeat expansion causes spinocerebellar ataxia type 2, while intermediate-length expansions also increase susceptibility to amyotrophic lateral sclerosis. This analysis covers 1,893 ATXN2 variants and mutations. Of these, 36% have computational variant effect predictions. Disease context includes spinocerebellar ataxia type 2, amyotrophic lateral sclerosis, and hypothyroidism. Example ATXN2 variants include R2C, R2H, and S3*.
Variant analysis overview
- Gene: ATXN2
- Protein: Ataxin-2
- UniProt accession: Q99700
- Organism: Homo sapiens
- Variants analyzed: 1893
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 1,607 unspecified-consequence records; 7 stop lost; 181 missense variants; 81 synonymous variants; 9 frameshift variants; 9 stop-gained variants; 2 stop retained variant; 5 in-frame deletions; 1 splice-region variants
- Prediction scores: 682 variants have prediction scores (36% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: spinocerebellar ataxia type 2, amyotrophic lateral sclerosis, hypothyroidism, Abnormality of the skeletal system, hypertensive disorder, coronary artery disorder, Thrombocytopenia, open-angle glaucoma, Hashimoto thyroiditis, Parkinson disease, rheumatoid arthritis, gout.
Protein structure and variant hotspots
- Protein features: 1 domains; 22 post-translational modification sites.
- Structural context: 65 variants have structural context.
- PTM context: 17 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable ATXN2 variants
Examples include R2C, R2H, S3*, S3P, A4E, A5T, A6S, A7P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- R2C (p.Arg2Cys), Ensembl rs1019391909, CADD 22.70
- R2H (p.Arg2His), gnomAD rs1208754584, CADD 20.10
- S3* (p.Ser3Ter), TOPMed rs1365416806, gnomAD rs1365416806, CADD 34.00
- S3P (p.Ser3Pro), Ensembl rs2135865416, CADD 13.70
- A4E (p.Ala4Glu), TOPMed rs1885159648, CADD 8.88
- A5T (p.Ala5Thr), rs1465546289, gnomAD rs1465546289, CADD 13.60, Variant assessed as somatic; moderate impact.
- A6S (p.Ala6Ser), TOPMed rs1385384243, gnomAD rs1385384243, CADD 17.50
- A7P (p.Ala7Pro), TOPMed rs973735194, gnomAD rs973735194, CADD 4.62
- P8L (p.Pro8Leu), TOPMed rs1885159064, CADD 13.50
- P8S (p.Pro8Ser), TOPMed rs1885159169, CADD 10.90
- R9P (p.Arg9Pro), TOPMed rs1441710563, gnomAD rs1441710563, CADD 14.20
- R9Q (p.Arg9Gln), TOPMed rs1441710563, gnomAD rs1441710563, CADD 2.76
- R9W (p.Arg9Trp), TOPMed rs1331860750, gnomAD rs1331860750, CADD 22.60
- S10R (p.Ser10Arg), 1000Genomes rs775766002, ExAC rs775766002, TOPMed rs775766002, gnomAD rs775766002, CADD 12.40
- P11H (p.Pro11His), TOPMed rs1355937464, CADD 16.10
- A12P (p.Ala12Pro), TOPMed rs1240873229, gnomAD rs1240873229, CADD 14.00
- V13G (p.Val13Gly), TOPMed rs1429950459, gnomAD rs1429950459, CADD 15.40
- A14S (p.Ala14Ser), TOPMed rs915579754, gnomAD rs915579754, CADD 13.70
- T15I (p.Thr15Ile), TOPMed rs1592947170, CADD 2.92, Uncertain significance
- T15S (p.Thr15Ser), TOPMed rs1592947170, CADD 4.03, Uncertain significance, Inborn genetic diseases
- E16D (p.Glu16Asp), TOPMed rs1885157378, CADD 13.10
- E16G (p.Glu16Gly), TOPMed rs992476955, gnomAD rs992476955, CADD 17.90
- E16K (p.Glu16Lys), TOPMed rs1419713183, gnomAD rs1419713183, CADD 13.90, Uncertain significance
- E16Q (p.Glu16Gln), rs1419713183, ClinGen CA386734601, ClinVar RCV004421157, TOPMed rs1419713183, CADD 11.40, Uncertain significance, Inborn genetic diseases
- E16V (p.Glu16Val), TOPMed rs992476955, gnomAD rs992476955, CADD 17.40
- S17C (p.Ser17Cys), TOPMed rs959774570, CADD 17.10
- R18G (p.Arg18Gly), TOPMed rs1885157132
- F20L (p.Phe20Leu), TOPMed rs1159788344, CADD 7.25
- A21T (p.Ala21Thr), gnomAD rs1226430967, CADD 15.90
- A23G (p.Ala23Gly), TOPMed rs998941502, CADD 16.60
- A23T (p.Ala23Thr), TOPMed rs1031423101, gnomAD rs1031423101, CADD 15.10
- R24S (p.Arg24Ser), rs1349716848, ClinGen CA386734517, ClinVar RCV004421160, TOPMed rs1349716848, CADD 15.90, Uncertain significance, Inborn genetic diseases
- R24T (p.Arg24Thr), TOPMed rs969300734, CADD 15.80
- W25* (p.Trp25Ter), TOPMed rs1885155750, CADD 35.00
- P26L (p.Pro26Leu), Ensembl rs1885155425, CADD 20.40
- P26S (p.Pro26Ser), Ensembl rs1885155582, CADD 17.20
- W28C (p.Trp28Cys), TOPMed rs1041056056, gnomAD rs1041056056, CADD 17.80, Uncertain significance, Inborn genetic diseases
- W28L (p.Trp28Leu), Ensembl rs1885154704, CADD 15.90, Uncertain significance, Inborn genetic diseases
- R29L (p.Arg29Leu), gnomAD rs1885154332, CADD 19.50
- S30L (p.Ser30Leu), cosmic curated COSV10822, CADD 21.60
- L31I (p.Leu31Ile), Ensembl rs1885153998, CADD 15.60
- Q32H (p.Gln32His), TOPMed rs1314318681, gnomAD rs1314318681, CADD 16.90
- R33Q (p.Arg33Gln), TOPMed rs1246856233, CADD 17.90
- R33W (p.Arg33Trp), cosmic curated COSV66483, TOPMed rs1338584860, gnomAD rs1338584860, CADD 22.60
- A35T (p.Ala35Thr), TOPMed rs1885153108, CADD 17.60
- A35V (p.Ala35Val), Ensembl rs1885152996, CADD 17.10
- R36L (p.Arg36Leu), TOPMed rs1265858055, CADD 12.90
- R36Q (p.Arg36Gln), TOPMed rs1265858055
- R37W (p.Arg37Trp), NCI-TCGA TCGA novel, CADD 18.80, Variant assessed as somatic; moderate impact.
- S38G (p.Ser38Gly), rs1885152002, ClinGen CA386734386, ClinVar RCV002688450, TOPMed rs1885152002, CADD 1.00, Uncertain significance, Inborn genetic diseases
- S38R (p.Ser38Arg), TOPMed rs1259513091, CADD 17.70
- G39R (p.Gly39Arg), TOPMed rs1885151664, CADD 17.20, Uncertain significance, Inborn genetic diseases
- G41D (p.Gly41Asp), TOPMed rs1262192397, gnomAD rs1262192397, CADD 21.40, PolyPhen-2 0.00
- G41S (p.Gly41Ser), Ensembl rs1885150883, CADD 23.10, PolyPhen-2 0.00
- G42A (p.Gly42Ala), TOPMed rs1253427273
- G42D (p.Gly42Asp), TOPMed rs1253427273, CADD 16.90
- G42R (p.Gly42Arg), TOPMed rs1182401488
- G43S (p.Gly43Ser), TOPMed rs1047179807, gnomAD rs1047179807, CADD 22.50, PolyPhen-2 0.01
- G43V (p.Gly43Val), TOPMed rs1885149944, CADD 22.30, PolyPhen-2 0.00
- G44D (p.Gly44Asp), TOPMed rs1566092029, CADD 10.20
- A45G (p.Ala45Gly), 1000Genomes rs1402668980, TOPMed rs1402668980, gnomAD rs1402668980, CADD 0.82
- A45S (p.Ala45Ser), gnomAD rs1244045344, CADD 10.00
- A46D (p.Ala46Asp), 1000Genomes rs770648742, ExAC rs770648742, gnomAD rs770648742, CADD 0.15
- A46G (p.Ala46Gly), 1000Genomes rs770648742, ExAC rs770648742, gnomAD rs770648742, CADD 0.03
- A46P (p.Ala46Pro), rs920435578, ClinGen CA243622442, ClinVar RCV002764847, 1000Genomes rs920435578, CADD 15.40, PolyPhen-2 0.01, Uncertain significance, Inborn genetic diseases
- A46T (p.Ala46Thr), 1000Genomes rs920435578, TOPMed rs920435578, gnomAD rs920435578, CADD 7.57, Uncertain significance
- A46V (p.Ala46Val), 1000Genomes rs770648742, ExAC rs770648742, gnomAD rs770648742, CADD 17.70, PolyPhen-2 0.01
- P47T (p.Pro47Thr), rs948625674, ClinGen CA243622439, ClinVar RCV002965224, ClinVar RCV004809945, CADD 4.07, Conflicting interpretations, Inborn genetic diseases; not provided
- G48A (p.Gly48Ala), rs1216505971, ClinGen CA386734288, ClinVar RCV004421142, TOPMed rs1216505971, CADD 0.59, Uncertain significance, Inborn genetic diseases
- G48E (p.Gly48Glu), TOPMed rs1216505971, gnomAD rs1216505971, CADD 10.20, Uncertain significance
- P49Q (p.Pro49Gln), rs1318202779, ClinGen CA386734279, ClinVar RCV004421143, TOPMed rs1318202779, CADD 15.60, Likely benign, Inborn genetic diseases
- P49S (p.Pro49Ser), TOPMed rs1371744210, gnomAD rs1371744210, CADD 11.40
- P51L (p.Pro51Leu), rs1202618139, ClinGen CA386734257, ClinVar RCV002733483, TOPMed rs1202618139, CADD 25.20, Uncertain significance, Inborn genetic diseases
- A53V (p.Ala53Val), TOPMed rs1253800220, gnomAD rs1253800220, CADD 22.60
- A54D (p.Ala54Asp), TOPMed rs1257412203, CADD 22.90
- A54T (p.Ala54Thr), TOPMed rs1202713228, CADD 22.10
- A54V (p.Ala54Val), TOPMed rs1257412203, CADD 21.20
- P55H (p.Pro55His), Ensembl rs1592946973, CADD 23.20
- P56L (p.Pro56Leu), TOPMed rs915859049, gnomAD rs915859049, CADD 23.20
- P56R (p.Pro56Arg), TOPMed rs915859049, gnomAD rs915859049
- P56S (p.Pro56Ser), TOPMed rs1426185120, CADD 22.80
- P56T (p.Pro56Thr), TOPMed rs1426185120, CADD 22.70
- P57L (p.Pro57Leu), TOPMed rs1390837161, gnomAD rs1390837161, CADD 22.40
- P57Q (p.Pro57Gln), TOPMed rs1390837161, gnomAD rs1390837161, CADD 23.40
- P57R (p.Pro57Arg), TOPMed rs1390837161, gnomAD rs1390837161, CADD 23.50
- P57S (p.Pro57Ser), gnomAD rs959703234, CADD 22.50
- P58A (p.Pro58Ala), Ensembl rs1592946932
- P58L (p.Pro58Leu), Ensembl rs2135864983, CADD 16.20
- P58S (p.Pro58Ser), Ensembl rs1592946932, CADD 14.20
- G59A (p.Gly59Ala), cosmic curated COSV10891, gnomAD rs1885144467, CADD 19.00
- G59C (p.Gly59Cys), Ensembl rs905904179, CADD 23.90, Uncertain significance, Inborn genetic diseases
- G59D (p.Gly59Asp), gnomAD rs1885144467, CADD 22.70
- G59R (p.Gly59Arg), cosmic curated COSV10530, Ensembl rs905904179, CADD 22.20, Uncertain significance
- P60A (p.Pro60Ala), gnomAD rs924331402, CADD 22.00, Uncertain significance
- P60L (p.Pro60Leu), gnomAD rs1488271827, CADD 23.30
- P60S (p.Pro60Ser), rs924331402, ClinGen CA243622429, ClinVar RCV002702401, gnomAD rs924331402, CADD 22.60, Uncertain significance, Inborn genetic diseases
- G61C (p.Gly61Cys), Ensembl rs1044375986
- G61R (p.Gly61Arg), cosmic curated COSV10530, Ensembl rs1044375986, CADD 23.10
- G61V (p.Gly61Val), gnomAD rs1386598096, CADD 23.00
- P62L (p.Pro62Leu), TOPMed rs1885143409, CADD 23.50
- P62S (p.Pro62Ser), rs1592946886, ClinGen CA386734149, ClinVar RCV002813000, Ensembl rs1592946886, CADD 22.40, Uncertain significance, Inborn genetic diseases
- P63A (p.Pro63Ala), TOPMed rs1183618784, gnomAD rs1183618784, CADD 22.10, Uncertain significance
- P63L (p.Pro63Leu), TOPMed rs1417848473, gnomAD rs1417848473, CADD 21.30
- P63S (p.Pro63Ser), TOPMed rs1183618784, gnomAD rs1183618784, CADD 22.60, Uncertain significance
- P63T (p.Pro63Thr), rs1183618784, ClinGen CA386734138, ClinVar RCV002911571, TOPMed rs1183618784, CADD 22.50, Uncertain significance, Inborn genetic diseases
- P64A (p.Pro64Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P64L (p.Pro64Leu), gnomAD rs1435423211, CADD 22.70, Uncertain significance, Inborn genetic diseases
- P64S (p.Pro64Ser), gnomAD rs1248246614, CADD 21.20
- S65F (p.Ser65Phe), TOPMed rs1290735356, gnomAD rs1290735356, CADD 21.80
- S65P (p.Ser65Pro), cosmic curated COSV10530, Ensembl rs1369238681
- S65T (p.Ser65Thr), Ensembl rs1369238681, CADD 16.40
- S65Y (p.Ser65Tyr), TOPMed rs1290735356, gnomAD rs1290735356, CADD 20.60
- R66P (p.Arg66Pro), cosmic curated COSV10530, gnomAD rs1566091838, CADD 15.30
- R66W (p.Arg66Trp), Ensembl rs1350840606, CADD 22.80
- Q67* (p.Gln67Ter), TOPMed rs968892056, gnomAD rs968892056, CADD 36.00
- Q67E (p.Gln67Glu), TOPMed rs968892056, gnomAD rs968892056
- Q67R (p.Gln67Arg), TOPMed rs1354881591, gnomAD rs1354881591, CADD 15.70
- P70H (p.Pro70His), gnomAD rs1477221359, CADD 23.50
- P70S (p.Pro70Ser), gnomAD rs1193252000, CADD 22.30
- P71L (p.Pro71Leu), TOPMed rs879391188, gnomAD rs879391188, CADD 18.60, Uncertain significance
- P71R (p.Pro71Arg), TOPMed rs879391188, gnomAD rs879391188, CADD 22.20, Uncertain significance
- P71S (p.Pro71Ser), Ensembl rs1885140308, CADD 23.10
- S72F (p.Ser72Phe), 1000Genomes rs536609944, ExAC rs536609944, TOPMed rs536609944, gnomAD rs536609944, CADD 22.30, Uncertain significance
- S72P (p.Ser72Pro), cosmic curated COSV10530, Ensembl rs1592946782, CADD 17.80
- S72Y (p.Ser72Tyr), 1000Genomes rs536609944, ExAC rs536609944, TOPMed rs536609944, gnomAD rs536609944, CADD 21.60, Uncertain significance
- A73P (p.Ala73Pro), gnomAD rs1380791606, CADD 18.40
- A73S (p.Ala73Ser), gnomAD rs1380791606, CADD 14.30, PolyPhen-2 0.22
- A73T (p.Ala73Thr), gnomAD rs1380791606, CADD 15.80, PolyPhen-2 0.30
- A73V (p.Ala73Val), 1000Genomes rs2135864780, CADD 18.20, PolyPhen-2 0.40
- S74L (p.Ser74Leu), TOPMed rs1008190781, gnomAD rs1008190781, CADD 21.70, Uncertain significance
- S74P (p.Ser74Pro), Ensembl rs1592946764, CADD 25.00
- D75E (p.Asp75Glu), gnomAD rs1315658955, CADD 22.90
- D75G (p.Asp75Gly), gnomAD rs1238343244, CADD 23.60
- C76Y (p.Cys76Tyr), TOPMed rs887112547, CADD 25.20
- C76Q (p.Cys76Gln), rs1286551180, gnomAD 12-111453660-GCA-, CADD 20.00
- C76C (p.Cys76Cys), gnomAD 12-111453660-G-A, CADD 21.80
- C76* (p.Cys76Ter), gnomAD 12-111453660-G-T, CADD 21.50
- C76F (p.Cys76Phe), gnomAD 12-111453661-C-A, CADD 21.00
- C76R (p.Cys76Arg), gnomAD 12-111453662-A-G, CADD 22.30
- F77L (p.Phe77Leu), gnomAD rs1269477208, CADD 25.80
- G78D (p.Gly78Asp), TOPMed rs1448276219, CADD 24.90
- G78R (p.Gly78Arg), TOPMed rs1374016546, CADD 22.60, PolyPhen-2 0.02
- G78S (p.Gly78Ser), TOPMed rs1374016546, CADD 24.90
- S79G (p.Ser79Gly), Ensembl rs1885138247, CADD 22.40
- S79N (p.Ser79Asn), TOPMed rs1312124600, gnomAD rs1312124600, CADD 22.70
- S79T (p.Ser79Thr), TOPMed rs1312124600, gnomAD rs1312124600, CADD 22.60
- N80I (p.Asn80Ile), Ensembl rs1885137888, CADD 24.20
- G81C (p.Gly81Cys), gnomAD rs1309865539, CADD 24.70, PolyPhen-2 0.67
- G81V (p.Gly81Val), gnomAD rs1279118019, CADD 22.90, PolyPhen-2 0.10
- N82D (p.Asn82Asp), gnomAD rs1392466485, CADD 21.40
- N82H (p.Asn82His), cosmic curated COSV10530
- N82K (p.Asn82Lys), 1000Genomes rs1220774408, TOPMed rs1220774408, gnomAD rs1220774408, CADD 21.90
- N82S (p.Asn82Ser), TOPMed rs1885137251, CADD 20.80
- G83C (p.Gly83Cys), gnomAD rs1365170103, CADD 23.30, PolyPhen-2 0.01
- G83D (p.Gly83Asp), ExAC rs777393909, TOPMed rs777393909, gnomAD rs777393909, CADD 23.30, PolyPhen-2 0.51
- G84C (p.Gly84Cys), Ensembl rs1885136407, CADD 20.80
- G84D (p.Gly84Asp), gnomAD rs1885136308, CADD 19.20
- G84R (p.Gly84Arg), Ensembl rs1885136407
- G85C (p.Gly85Cys), cosmic curated COSV66485, CADD 25.30, PolyPhen-2 0.66
- G85S (p.Gly85Ser), gnomAD rs1402751177, CADD 15.30
- A86T (p.Ala86Thr), Ensembl rs866750676, CADD 18.20
- A86V (p.Ala86Val), gnomAD rs1037925868, CADD 15.60
- A86E (p.Ala86Glu), gnomAD 12-111453670-G-T, CADD 16.00
- R88L (p.Arg88Leu), cosmic curated COSV66482, CADD 20.90
- R88Q (p.Arg88Gln), TOPMed rs1366993433, gnomAD rs1366993433, CADD 23.00
- P89L (p.Pro89Leu), cosmic curated COSV66485, gnomAD rs1318594762, CADD 19.10
- G90C (p.Gly90Cys), 1000Genomes rs1885134947, TOPMed rs1885134947, CADD 22.50
- G90S (p.Gly90Ser), 1000Genomes rs1885134947, TOPMed rs1885134947, CADD 17.00
- G90V (p.Gly90Val), gnomAD rs948619967, CADD 17.70
- G90G (p.Gly90Gly), gnomAD 12-111453654-G-A, CADD 21.80
- G90A (p.Gly90Ala), gnomAD 12-111453654-GC-G, CADD 19.50
- G90D (p.Gly90Asp), rs1369005573, gnomAD 12-111453655-C-T, CADD 21.40
- S91C (p.Ser91Cys), TOPMed rs1885134709
- S91F (p.Ser91Phe), TOPMed rs1885134709, CADD 9.23
- S91S (p.Ser91Ser), rs749706608, gnomAD 12-111453630-A-C, CADD 20.50
- R92P (p.Arg92Pro), Ensembl rs2135864564
- R92R (p.Arg92Arg), gnomAD 12-111453657-C-T, CADD 21.70
- R92M (p.Arg92Met), gnomAD 12-111453658-C-A, CADD 21.40
- R92K (p.Arg92Lys), gnomAD 12-111453658-C-T, CADD 21.80
- R92G (p.Arg92Gly), rs1227849917, gnomAD 12-111453659-T-C, CADD 22.40
Public ATXN2 analysis runs
- ATXN2 analysis run — ATXN2 (1,893 variants) — completed 2026-08-22