SETX (Helicase senataxin) variants and mutations
SETX (also known as Helicase senataxin) is a human protein-coding gene encoding a helicase senataxin protein. It resolves RNA-DNA hybrids and supports transcription termination, RNA processing, and genome stability, particularly in long-lived neurons. Different pathogenic mechanisms cause ataxia with oculomotor apraxia type 2 or juvenile amyotrophic lateral sclerosis type 4. This analysis covers 3,603 SETX variants and mutations. Of these, 76% have computational variant effect predictions. Disease context includes spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, amyotrophic lateral sclerosis type 4, and Spinocerebellar ataxia with axonal neuropathy type 2. Example SETX variants include S2G, S2R, and T3A.
Variant analysis overview
- Gene: SETX
- Protein: Helicase senataxin
- UniProt accession: Q7Z333
- Organism: Homo sapiens
- Variants analyzed: 3603
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 3,251 unspecified-consequence records; 142 synonymous variants; 6 stop-gained variants; 11 in-frame deletions; 157 missense variants; 28 frameshift variants; 4 in-frame insertions; 1 splice-region variants; 4 substitution
- Prediction scores: 2,727 variants have prediction scores (76% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, amyotrophic lateral sclerosis type 4, Spinocerebellar ataxia with axonal neuropathy type 2, hereditary disease, neurodegenerative disease, cerebellar ataxia, distal hereditary motor neuropathy, amyotrophic lateral sclerosis, frontotemporal dementia, spastic ataxia, Abnormal central motor function, Ataxia - oculomotor apraxia type 1.
Protein structure and variant hotspots
- Protein features: 2 domains; 3 binding sites; 15 post-translational modification sites.
- Structural context: 573 variants have structural context.
- PTM context: 16 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, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable SETX variants
Examples include S2G, S2R, T3A, T3I, C4R, C5S, W6L, C7Y. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2G (p.Ser2Gly), rs149808180, ClinGen CA5298157, ClinVar RCV000585415, ClinVar RCV001860113, REVEL 0.31, CADD 26.80, Conflicting interpretations, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- S2R (p.Ser2Arg), ExAC rs756610906, TOPMed rs756610906, gnomAD rs756610906, REVEL 0.46, CADD 25.50
- T3A (p.Thr3Ala), Ensembl rs1848488166, REVEL 0.39, CADD 25.80
- T3I (p.Thr3Ile), rs28941475, ClinGen CA252185, ClinVar RCV000002380, ClinVar RCV000414273, AlphaMissense 0.54, MetaLR 0.63, Likely pathogenic, not provided
- C4R (p.Cys4Arg), NCI-TCGA TCGA novel, REVEL 0.80, CADD 28.70, Variant assessed as somatic; moderate impact.
- C5S (p.Cys5Ser), rs1589791895, ClinGen CA375352133, ClinVar RCV000813622, TOPMed rs1589791895, REVEL 0.34, CADD 22.90, Uncertain significance, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- W6L (p.Trp6Leu), TOPMed rs1848487351, REVEL 0.67, CADD 30.00
- C7Y (p.Cys7Tyr), Ensembl rs940872563
- T8M (p.Thr8Met), rs1057520367, ClinGen CA16605391, NCI-TCGA Cosmic COSV5638, ClinVar RCV000440159, AlphaMissense 0.37, MetaLR 0.83, Pathogenic, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
- P9L (p.Pro9Leu), rs1350139497, ClinGen CA375352104, ClinVar RCV002437389, TOPMed rs1350139497, REVEL 0.49, CADD 24.30, Uncertain significance, Inborn genetic diseases
- P9S (p.Pro9Ser), rs200979931, ClinGen CA200838334, ClinVar RCV003085811, gnomAD rs200979931, REVEL 0.39, CADD 24.50, Uncertain significance, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- G10D (p.Gly10Asp), Ensembl rs1848486034, REVEL 0.46, CADD 23.20
- G10R (p.Gly10Arg), ExAC rs751146499, REVEL 0.44, CADD 23.10
- G10V (p.Gly10Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G11D (p.Gly11Asp), rs886063560, ClinGen CA10626642, ClinVar RCV000268908, ClinVar RCV000323745, AlphaMissense 0.59, MetaLR 0.66, Uncertain significance, Amyotrophic lateral sclerosis type 4; not provided; Spinocerebellar ataxia, auto
- A12S (p.Ala12Ser), rs763609145, ClinGen CA5298150, ClinVar RCV003797792, ClinVar RCV006454485, REVEL 0.30, CADD 0.00, Conflicting interpretations, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- S13F (p.Ser13Phe), ExAC rs762432813, TOPMed rs762432813, gnomAD rs762432813, REVEL 0.41, CADD 24.20, Uncertain significance, Inborn genetic diseases
- S13Y (p.Ser13Tyr), NCI-TCGA Cosmic COSV5637, Variant assessed as somatic; moderate impact.
- T14A (p.Thr14Ala), ExAC rs775065109, gnomAD rs775065109, REVEL 0.23, CADD 15.40
- T14I (p.Thr14Ile), TOPMed rs770310239, gnomAD rs770310239, REVEL 0.39, CADD 23.80
- I15F (p.Ile15Phe), rs151040199, ClinGen CA5298145, ClinVar RCV002333717, ClinVar RCV003102579, REVEL 0.25, CADD 0.03, Conflicting interpretations, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
- I15M (p.Ile15Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I15S (p.Ile15Ser), ExAC rs770780238, gnomAD rs770780238, REVEL 0.23, CADD 13.00
- I15V (p.Ile15Val), rs151040199, ClinGen CA5298146, ClinVar RCV001848122, ClinVar RCV002034741, REVEL 0.25, CADD 0.00, Conflicting interpretations, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
- D16E (p.Asp16Glu), gnomAD rs1354676019, REVEL 0.12, CADD 8.67
- D16G (p.Asp16Gly), TOPMed rs1246552404, gnomAD rs1246552404, REVEL 0.35, CADD 22.90
- F17L (p.Phe17Leu), rs2539259741, ClinGen CA375352066, ClinVar RCV003136627, REVEL 0.45, CADD 18.10, Uncertain significance, not provided
- K19R (p.Lys19Arg), gnomAD rs1848483700, REVEL 0.24, CADD 14.50
- R20C (p.Arg20Cys), rs200228952, ClinGen CA5298142, ClinVar RCV002355689, ClinVar RCV002473370, REVEL 0.18, CADD 8.70, Conflicting interpretations, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- R20H (p.Arg20His), rs79740039, ClinGen CA048242, ClinVar RCV000144869, ClinVar RCV000327408, REVEL 0.16, CADD 3.28, Benign/Likely benign, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
- Y21C (p.Tyr21Cys), rs780157648, ClinGen CA5298140, ClinVar RCV003785771, ExAC rs780157648, REVEL 0.55, CADD 24.90, Likely benign, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- Y21H (p.Tyr21His), TOPMed rs1848482853, gnomAD rs1848482853, REVEL 0.48, CADD 24.60
- A22S (p.Ala22Ser), rs756600708, ClinGen CA375352034, ClinVar RCV000644832, ExAC rs756600708, AlphaMissense 0.18, MetaLR 0.73, Uncertain significance, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- A22T (p.Ala22Thr), rs756600708, ClinGen CA5298139, ClinVar RCV001350040, ExAC rs756600708, REVEL 0.37, AlphaMissense 0.18, Benign, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- S23F (p.Ser23Phe), rs1323126988, ClinGen CA375352025, ClinVar RCV000547708, TOPMed rs1323126988, REVEL 0.20, CADD 21.70, Likely benign, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
- N24D (p.Asn24Asp), TOPMed rs1403460462, gnomAD rs1403460462, REVEL 0.11, CADD 6.67, Uncertain significance, not specified
- N24H (p.Asn24His), TOPMed rs1403460462, gnomAD rs1403460462
- N24K (p.Asn24Lys), Ensembl rs1848481750, REVEL 0.10, CADD 0.31
- N24S (p.Asn24Ser), rs981346599, ClinGen CA200838232, ClinVar RCV000531183, ClinVar RCV003233735, REVEL 0.21, CADD 0.16, Uncertain significance, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
- P26L (p.Pro26Leu), rs377617692, ClinGen CA5298138, ClinVar RCV001848131, ClinVar RCV003120722, REVEL 0.26, AlphaMissense 0.07, Conflicting interpretations, Inborn genetic diseases; not provided; Hereditary spastic paraplegia
- P26R (p.Pro26Arg), rs377617692, ClinGen CA10629250, ClinVar RCV000312389, ClinVar RCV000408198, AlphaMissense 0.07, MetaLR 0.20, Uncertain significance, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- S27F (p.Ser27Phe), rs374733340, ClinGen CA5298136, NCI-TCGA Cosmic COSV5638, ClinVar RCV002998767, REVEL 0.25, CADD 21.60, Conflicting interpretations, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- G28A (p.Gly28Ala), rs1848480573, ClinGen CA375351999, ClinVar RCV002727680, AlphaMissense 0.09, MetaLR 0.29, Uncertain significance, Inborn genetic diseases
- G28D (p.Gly28Asp), Ensembl rs1848480573
- E29G (p.Glu29Gly), Ensembl rs1848480428
- Q31E (p.Gln31Glu), TOPMed rs1848480287, REVEL 0.20, CADD 9.90
- Q31H (p.Gln31His), 1000Genomes rs201795631, ExAC rs201795631, TOPMed rs201795631, gnomAD rs201795631, REVEL 0.28, CADD 0.09, Benign, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
- Q31R (p.Gln31Arg), rs1564165988, ClinGen CA375351976, ClinVar RCV003788821, TOPMed rs1564165988, REVEL 0.09, CADD 12.00, Benign, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- T32I (p.Thr32Ile), TOPMed rs1332915918, REVEL 0.33, CADD 23.10
- T32R (p.Thr32Arg), TOPMed rs1332915918, Uncertain significance, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
- D34G (p.Asp34Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D34N (p.Asp34Asn), rs555364587, ClinGen CA5298131, ClinVar RCV003482861, 1000Genomes rs555364587, REVEL 0.14, CADD 0.12, Uncertain significance, not provided
- E35G (p.Glu35Gly), Ensembl rs2131575493
- E35K (p.Glu35Lys), rs759394055, NCI-TCGA Cosmic COSV9980, ExAC rs759394055, TOPMed rs759394055, REVEL 0.48, CADD 24.80, Variant assessed as somatic; moderate impact.
- Y39F (p.Tyr39Phe), TOPMed rs1255659172, gnomAD rs1255659172, REVEL 0.45, CADD 26.20
- Y39H (p.Tyr39His), gnomAD rs1229540765, REVEL 0.53, CADD 27.50
- C40F (p.Cys40Phe), Ensembl rs1351719244
- L41F (p.Leu41Phe), 1000Genomes rs188406893, ESP rs188406893, ExAC rs188406893, TOPMed rs188406893, REVEL 0.43, CADD 14.10, Uncertain significance, not provided
- E42Q (p.Glu42Gln), NCI-TCGA Cosmic COSV9980, Variant assessed as somatic; moderate impact.
- E46D (p.Glu46Asp), Ensembl rs1564165848, REVEL 0.48, CADD 10.70
- H48N (p.His48Asn), NCI-TCGA Cosmic COSV5639, Variant assessed as somatic; moderate impact.
- H48Y (p.His48Tyr), Ensembl rs1848477577
- K49I (p.Lys49Ile), ESP rs142551293, ExAC rs142551293, TOPMed rs142551293, gnomAD rs142551293, Uncertain significance
- K49R (p.Lys49Arg), rs142551293, ClinGen CA5298125, ClinVar RCV001287948, ClinVar RCV003166620, REVEL 0.10, CADD 16.20, Conflicting interpretations, Inborn genetic diseases; not provided; Spinocerebellar ataxia, autosomal recessi
- A50G (p.Ala50Gly), ExAC rs746570656, TOPMed rs746570656, gnomAD rs746570656, REVEL 0.41, CADD 26.40
- R51K (p.Arg51Lys), rs777256092, ClinGen CA200838145, ClinVar RCV001770649, ClinVar RCV002543999, REVEL 0.40, CADD 25.40, Uncertain significance, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- D52G (p.Asp52Gly), TOPMed rs1848476749, REVEL 0.42, CADD 32.00
- E53G (p.Glu53Gly), ExAC rs769847544, gnomAD rs769847544, REVEL 0.24, CADD 22.90
- L54F (p.Leu54Phe), gnomAD rs1175429740, REVEL 0.34, CADD 22.10, Likely benign
- P55S (p.Pro55Ser), rs746388055, NCI-TCGA Cosmic COSV9980, ExAC rs746388055, gnomAD rs746388055, REVEL 0.47, CADD 25.40, Variant assessed as somatic; moderate impact.
- F56S (p.Phe56Ser), rs1032816797, ClinGen CA200838130, ClinVar RCV001056142, TOPMed rs1032816797, REVEL 0.14, CADD 9.15, Uncertain significance, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- L57S (p.Leu57Ser), Ensembl rs868232992
- H58D (p.His58Asp), ExAC rs757760067, TOPMed rs757760067, gnomAD rs757760067, REVEL 0.58, CADD 26.80, Likely benign
- H58R (p.His58Arg), rs2539258376, ClinGen CA375351791, ClinVar RCV003792743, Uncertain significance, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- H58Y (p.His58Tyr), rs757760067, ClinGen CA200838114, ClinVar RCV001049138, ClinVar RCV002404330, REVEL 0.53, CADD 26.00, Conflicting interpretations, Inborn genetic diseases; not provided; Amyotrophic lateral sclerosis type 4
- V60I (p.Val60Ile), TOPMed rs1445955234, REVEL 0.12, CADD 17.80
- W62G (p.Trp62Gly), ExAC rs769895120, REVEL 0.65, CADD 29.70
- E65K (p.Glu65Lys), rs1554825315, ClinGen CA375351730, ClinVar RCV000790206, ClinVar RCV002298772, REVEL 0.68, CADD 26.30, Uncertain significance, Charcot-Marie-Tooth disease
- T66A (p.Thr66Ala), TOPMed rs1848296771, REVEL 0.36, CADD 26.00
- T66I (p.Thr66Ile), rs776664916, ClinGen CA5298103, ClinVar RCV003804712, ExAC rs776664916, AlphaMissense 0.27, MetaLR 0.58, Likely benign, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- R68C (p.Arg68Cys), rs771481623, ClinGen CA5298102, ClinVar RCV001799572, ClinVar RCV003772202, REVEL 0.69, CADD 31.00, Conflicting interpretations, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
- R68G (p.Arg68Gly), ExAC rs771481623, TOPMed rs771481623, gnomAD rs771481623, REVEL 0.70, CADD 28.90, Likely pathogenic
- R68H (p.Arg68His), NCI-TCGA TCGA novel, TOPMed rs1777745223, REVEL 0.62, CADD 26.60, Variant assessed as somatic; moderate impact.
- L69V (p.Leu69Val), TOPMed rs1227986427, gnomAD rs1227986427, REVEL 0.37, CADD 25.40
- I70R (p.Ile70Arg), TOPMed rs899867518, gnomAD rs899867518, REVEL 0.66, CADD 24.90
- I70V (p.Ile70Val), rs747469176, ClinGen CA5298101, ClinVar RCV000644809, ClinVar RCV002422333, REVEL 0.17, CADD 8.63, Conflicting interpretations, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- N71K (p.Asn71Lys), NCI-TCGA Cosmic COSV5638, Variant assessed as somatic; moderate impact.
- H72L (p.His72Leu), gnomAD rs1294935001, REVEL 0.47, CADD 23.50
- H72N (p.His72Asn), TOPMed rs1378691553, gnomAD rs1378691553, REVEL 0.31, CADD 23.70
- H72Q (p.His72Gln), TOPMed rs939285966, gnomAD rs939285966, REVEL 0.27, CADD 20.10
- F73I (p.Phe73Ile), TOPMed rs1848295072, gnomAD rs1848295072, REVEL 0.38, CADD 22.00
- E74G (p.Glu74Gly), gnomAD rs1378361041, REVEL 0.48, CADD 26.30
- S76I (p.Ser76Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- M77V (p.Met77Val), TOPMed rs1275546682, gnomAD rs1275546682, REVEL 0.27, CADD 22.70
- I81T (p.Ile81Thr), TOPMed rs1848292572
- I81V (p.Ile81Val), rs371166895, ClinGen CA5298099, ClinVar RCV002450385, ClinVar RCV003482412, REVEL 0.11, CADD 15.70, Conflicting interpretations, Inborn genetic diseases; not provided; Spinocerebellar ataxia, autosomal recessi
- G82E (p.Gly82Glu), rs201864041, ClinGen CA5298096, ClinVar RCV001367166, ClinVar RCV002456568, REVEL 0.15, CADD 12.10, Conflicting interpretations, Inborn genetic diseases; Amyotrophic lateral sclerosis type 4; Spinocerebellar a
- G82V (p.Gly82Val), 1000Genomes rs201864041, ExAC rs201864041, TOPMed rs201864041, gnomAD rs201864041, REVEL 0.37, CADD 22.70, Benign
- D83E (p.Asp83Glu), Ensembl rs1047186938
- D84G (p.Asp84Gly), ExAC rs753447156, gnomAD rs753447156, REVEL 0.45, CADD 25.10
- D84V (p.Asp84Val), ExAC rs753447156, gnomAD rs753447156, REVEL 0.53, CADD 25.40
- D85N (p.Asp85Asn), rs2539240284, ClinGen CA375351594, ClinVar RCV004455598, Uncertain significance, Inborn genetic diseases
- E86D (p.Glu86Asp), Ensembl rs2131558179
- L87F (p.Leu87Phe), NCI-TCGA Cosmic COSV9981, REVEL 0.48, CADD 16.80, Variant assessed as somatic; moderate impact.
- L87I (p.Leu87Ile), gnomAD rs1424701796, REVEL 0.27, CADD 22.60
- Y88C (p.Tyr88Cys), rs149276791, ClinGen CA5298093, ClinVar RCV000698387, ClinVar RCV004659180, REVEL 0.63, CADD 26.00, Conflicting interpretations, Inborn genetic diseases; Amyotrophic lateral sclerosis type 4; Spinocerebellar a
- Y88H (p.Tyr88His), ExAC rs779659472, gnomAD rs779659472, REVEL 0.52, CADD 25.70
- I89M (p.Ile89Met), rs767232097, ClinGen CA5298091, ClinVar RCV001219943, ClinVar RCV002562491, REVEL 0.50, CADD 23.10, Conflicting interpretations, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- I89T (p.Ile89Thr), ExAC rs750309909, gnomAD rs750309909, REVEL 0.56, CADD 25.30, Uncertain significance, not provided
- I89V (p.Ile89Val), TOPMed rs1848290219, REVEL 0.31, CADD 23.50
- V90A (p.Val90Ala), gnomAD rs1208136830, REVEL 0.51, CADD 25.10
- D91G (p.Asp91Gly), rs1327343862, ClinGen CA375351550, ClinVar RCV000999255, gnomAD rs1327343862, REVEL 0.65, CADD 25.50, Uncertain significance, not provided
- N92D (p.Asn92Asp), ExAC rs761725435, TOPMed rs761725435, gnomAD rs761725435, REVEL 0.09, CADD 16.40
- N92S (p.Asn92Ser), ExAC rs751308926, TOPMed rs751308926, gnomAD rs751308926, REVEL 0.15, CADD 13.90
- N93D (p.Asn93Asp), 1000Genomes rs556595526, ExAC rs556595526, gnomAD rs556595526, REVEL 0.23, CADD 16.90
- N93S (p.Asn93Ser), TOPMed rs1421119656, REVEL 0.26, CADD 20.10
- E95Q (p.Glu95Gln), TOPMed rs974223555
- L98P (p.Leu98Pro), ExAC rs759736109, TOPMed rs759736109, gnomAD rs759736109, REVEL 0.52, CADD 22.00
- F99C (p.Phe99Cys), TOPMed rs962992307, gnomAD rs962992307, REVEL 0.36, CADD 22.70, Uncertain significance, Inborn genetic diseases
- D100G (p.Asp100Gly), gnomAD rs1365774411, REVEL 0.21, CADD 15.90
- I101V (p.Ile101Val), rs376848704, ClinGen CA5298086, ClinVar RCV001315431, ESP rs376848704, REVEL 0.13, CADD 15.00, Benign, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- T102A (p.Thr102Ala), rs770962447, ClinGen CA5298085, ClinVar RCV001848119, ClinVar RCV002034740, REVEL 0.08, CADD 16.10, Conflicting interpretations, Inborn genetic diseases; Spinocerebellar ataxia, autosomal recessive, with axona
- T102I (p.Thr102Ile), ESP rs372956007, ExAC rs372956007, gnomAD rs372956007, REVEL 0.24, CADD 21.30
- T102P (p.Thr102Pro), ExAC rs770962447, TOPMed rs770962447, gnomAD rs770962447, REVEL 0.34, CADD 23.10, Likely benign
- G103V (p.Gly103Val), TOPMed rs1848286889
- G103W (p.Gly103Trp), TOPMed rs1848287030
- Q104K (p.Gln104Lys), TOPMed rs1848286612
- F106S (p.Phe106Ser), NCI-TCGA Cosmic COSV5638, Variant assessed as somatic; moderate impact.
- E107D (p.Glu107Asp), Ensembl rs1848286185
- R111* (p.Arg111Ter), rs1451908310, ClinGen CA375351227, ClinVar RCV002949307, ClinVar RCV005254650, CADD 38.00, Pathogenic
- R111Q (p.Arg111Gln), NCI-TCGA Cosmic COSV5638, Ensembl rs1848285282, REVEL 0.43, CADD 26.70, Variant assessed as somatic; moderate impact.
- P113S (p.Pro113Ser), rs2539238950, ClinGen CA375351211, NCI-TCGA Cosmic COSV5639, ClinVar RCV002451815, Uncertain significance, Inborn genetic diseases
- L114F (p.Leu114Phe), gnomAD rs1188017352, REVEL 0.41, CADD 24.50
- L114S (p.Leu114Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L115H (p.Leu115His), TOPMed rs1848284240, REVEL 0.50, CADD 26.80
- L115V (p.Leu115Val), rs538372427, ClinGen CA5298080, ClinVar RCV001267159, ClinVar RCV001880135, REVEL 0.37, CADD 23.70, Conflicting interpretations, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- E116K (p.Glu116Lys), ExAC rs768443727, gnomAD rs768443727, REVEL 0.67, CADD 27.70
- I117M (p.Ile117Met), TOPMed rs1338835422, gnomAD rs1338835422, REVEL 0.50, CADD 23.20, Uncertain significance, not provided
- P121T (p.Pro121Thr), TOPMed rs1848283060
- Y122H (p.Tyr122His), TOPMed rs1734148458
- L123V (p.Leu123Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L124I (p.Leu124Ile), rs1488062133, ClinGen CA375351076, ClinVar RCV001665124, gnomAD rs1488062133, AlphaMissense 0.46, MetaLR 0.52, Uncertain significance, not provided
- L124V (p.Leu124Val), gnomAD rs1488062133, REVEL 0.34, AlphaMissense 0.46, Uncertain significance
- L125I (p.Leu125Ile), TOPMed rs1206306151, gnomAD rs1206306151, REVEL 0.35, CADD 25.60
- L125Q (p.Leu125Gln), TOPMed rs1326253334
- L125R (p.Leu125Arg), TOPMed rs1326253334
- H126N (p.His126Asn), TOPMed rs1198292384, gnomAD rs1198292384, REVEL 0.32, CADD 23.50
- H126P (p.His126Pro), rs368932301, ClinGen CA5298077, ClinVar RCV002474456, ClinVar RCV006559483, REVEL 0.59, CADD 26.00, Uncertain significance, not provided; Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, auto
- H126R (p.His126Arg), rs368932301, ClinGen CA5298078, ClinVar RCV001093201, ClinVar RCV001242996, REVEL 0.54, CADD 25.30, Conflicting interpretations, not provided; Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, auto
- E127D (p.Glu127Asp), rs1296707786, ClinGen CA375351024, ClinVar RCV001508274, gnomAD rs1296707786, REVEL 0.31, CADD 23.20, Uncertain significance, not provided
- R128C (p.Arg128Cys), rs552476047, ClinGen CA5298076, ClinVar RCV001311800, ClinVar RCV001871780, REVEL 0.55, CADD 31.00, Conflicting interpretations, not provided; Spinocerebellar ataxia, autosomal recessive, with axonal neuropath
- R128H (p.Arg128His), rs749887957, ClinGen CA5298075, NCI-TCGA Cosmic COSV9981, ClinVar RCV000516255, REVEL 0.15, CADD 20.70, Uncertain significance, not specified
- R128S (p.Arg128Ser), NCI-TCGA Cosmic COSV5638, NCI-TCGA Cosmic COSV5639, Variant assessed as somatic; moderate impact.
- N130K (p.Asn130Lys), ESP rs138363625, ExAC rs138363625, TOPMed rs138363625, gnomAD rs138363625, Likely benign
- N130T (p.Asn130Thr), rs1848058133, ClinGen CA375350503, ClinVar RCV002366384, TOPMed rs1848058133, AlphaMissense 0.28, MetaLR 0.21, Uncertain significance, Inborn genetic diseases
- E131K (p.Glu131Lys), rs758244236, NCI-TCGA Cosmic COSV5638, ExAC rs758244236, TOPMed rs758244236, AlphaMissense 0.24, MetaLR 0.49, Variant assessed as somatic; moderate impact.
- C133G (p.Cys133Gly), rs766625711, ClinGen CA375350484, ClinVar RCV001167589, ClinVar RCV001167590, REVEL 0.70, CADD 29.00, Uncertain significance, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- C133R (p.Cys133Arg), ExAC rs766625711, gnomAD rs766625711, REVEL 0.79, CADD 27.40, Uncertain significance
- E135D (p.Glu135Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E135G (p.Glu135Gly), TOPMed rs1848056674
- A136T (p.Ala136Thr), NCI-TCGA Cosmic COSV9980, Variant assessed as somatic; moderate impact.
- A136V (p.Ala136Val), rs750537710, ClinGen CA5298043, ClinVar RCV002323102, ClinVar RCV003094510, REVEL 0.24, CADD 22.30, Conflicting interpretations, Inborn genetic diseases; Spinocerebellar ataxia, autosomal recessive, with axona
- L137V (p.Leu137Val), TOPMed rs1403462469, REVEL 0.29, CADD 24.30, Uncertain significance, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- R139Q (p.Arg139Gln), Ensembl rs1848056207, REVEL 0.40, CADD 26.30
- R139W (p.Arg139Trp), rs960076085, NCI-TCGA Cosmic COSV5638, TOPMed rs960076085, REVEL 0.48, CADD 32.00, Variant assessed as somatic; moderate impact.
- Q142E (p.Gln142Glu), Ensembl rs1848056045
- A143S (p.Ala143Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N144D (p.Asn144Asp), TOPMed rs1589775185, REVEL 0.34, CADD 26.00
- N144S (p.Asn144Ser), rs767453182, ClinGen CA5298042, ClinVar RCV000644846, ClinVar RCV001167587, REVEL 0.30, CADD 24.30, Conflicting interpretations, Inborn genetic diseases; not specified; Amyotrophic lateral sclerosis type 4
- S146F (p.Ser146Phe), rs1286335620, TOPMed rs1286335620, gnomAD rs1286335620, REVEL 0.50, CADD 28.00, Variant assessed as somatic; moderate impact.
- S146P (p.Ser146Pro), gnomAD rs1408316133, REVEL 0.34, CADD 23.20
- Q148H (p.Gln148His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V149E (p.Val149Glu), TOPMed rs1589775141, gnomAD rs1589775141, REVEL 0.70, CADD 27.80
- V149M (p.Val149Met), TOPMed rs1848055104
- D151N (p.Asp151Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P154R (p.Pro154Arg), TOPMed rs1395595282, gnomAD rs1395595282, REVEL 0.62, CADD 27.20
- Y157C (p.Tyr157Cys), rs775967851, ClinGen CA5298037, ClinVar RCV002785463, ExAC rs775967851, REVEL 0.61, CADD 28.00, Uncertain significance, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
- L158F (p.Leu158Phe), gnomAD rs1339485543, REVEL 0.48, CADD 23.30
- L158V (p.Leu158Val), rs145438764, ClinGen CA5298036, ClinVar RCV000350037, ClinVar RCV000399144, REVEL 0.44, CADD 23.40, Conflicting interpretations, Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessiv
- F159L (p.Phe159Leu), rs1473646250, ClinGen CA375350292, ClinVar RCV001915019, gnomAD rs1473646250, REVEL 0.44, CADD 20.20, Benign, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2; Amyotroph
Public SETX analysis runs
- SETX analysis run — SETX (3,603 variants) — completed 2026-08-22