SPTA1 (P02549) variants and mutations
SPTA1 (also known as P02549) is a human protein-coding gene encoding a spectrin alpha chain, erythrocytic 1 protein. It forms the alpha-spectrin lattice underlying the red-blood-cell membrane and provides elasticity needed to survive repeated passage through the circulation. Pathogenic variants cause hereditary elliptocytosis, hereditary spherocytosis, or severe hereditary pyropoikilocytosis. This analysis covers 4,239 SPTA1 variants and mutations. Of these, 63% have computational variant effect predictions. Disease context includes elliptocytosis 2, Pyropoikilocytosis, and hereditary spherocytosis type 3. Example SPTA1 variants include M1L, E2K, and E2V.
Variant analysis overview
- Gene: SPTA1
- Protein: P02549
- UniProt accession: P02549
- Organism: Homo sapiens
- Variants analyzed: 4239
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 4,049 unspecified-consequence records; 1 stop retained variant; 87 synonymous variants; 83 missense variants; 6 splice-region variants; 1 in-frame deletions; 10 frameshift variants; 3 stop-gained variants
- Prediction scores: 2,651 variants have prediction scores (63% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: elliptocytosis 2, Pyropoikilocytosis, hereditary spherocytosis type 3, pyropoikilocytosis, hereditary, hereditary elliptocytosis, hereditary spherocytosis, Congenital hemolytic anemia, familial hemolytic anemia, Spherocytosis, hydrops fetalis, Decreased total leukocyte count, lysinuric protein intolerance.
Protein structure and variant hotspots
- Protein features: 4 domains; 8 binding sites; 2 post-translational modification sites.
- Structural context: 376 variants have structural context.
- PTM context: 2 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 SPTA1 variants
Examples include M1L, E2K, E2V, Q3K, Q3P, F4L, P5S, K6N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs1655190972, ClinGen CA343027438, ClinVar RCV003138697, Uncertain significance, not provided
- E2K (p.Glu2Lys), cosmic curated COSV10529, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E2V (p.Glu2Val), ExAC rs750427416, gnomAD rs750427416, CADD 17.70, PolyPhen-2 0.00
- Q3K (p.Gln3Lys), ExAC rs764788757, gnomAD rs764788757, CADD 0.44, PolyPhen-2 0.00
- Q3P (p.Gln3Pro), ExAC rs761277927, TOPMed rs761277927, gnomAD rs761277927, CADD 8.08, PolyPhen-2 0.00, Uncertain significance, not specified
- F4L (p.Phe4Leu), rs753495645, ClinGen CA1184299, ClinVar RCV000262000, ClinVar RCV000320939, CADD 0.28, PolyPhen-2 0.00, Uncertain significance, Pyropoikilocytosis, hereditary; Hereditary spherocytosis type 3; not specified
- P5S (p.Pro5Ser), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, NCI-TCGA Cosmic COSV6375, Variant assessed as somatic; moderate impact.
- K6N (p.Lys6Asn), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63753, Variant assessed as somatic; moderate impact.
- K6R (p.Lys6Arg), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, Variant assessed as somatic; moderate impact.
- E7K (p.Glu7Lys), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63753, Ensembl rs2101962645, Variant assessed as somatic; moderate impact.
- T8=, rs377733228, NCI-TCGA Cosmic COSV6375, Variant assessed as somatic; low impact.
- T8I (p.Thr8Ile), cosmic curated COSV10746, ExAC rs763682137, TOPMed rs763682137, gnomAD rs763682137, CADD 18.20, PolyPhen-2 0.00, Uncertain significance, not specified
- T8S (p.Thr8Ser), TOPMed rs1655189402, gnomAD rs1655189402, CADD 15.60, PolyPhen-2 0.00
- V9F (p.Val9Phe), rs111321033, ClinGen CA1184272, ClinVar RCV000309368, ClinVar RCV000364094, CADD 22.70, PolyPhen-2 0.10, Uncertain significance, not provided; Hereditary spherocytosis type 3; Pyropoikilocytosis, hereditary
- V9G (p.Val9Gly), gnomAD rs1655099008, CADD 21.30, PolyPhen-2 0.03
- V9I (p.Val9Ile), 1000Genomes rs111321033, ESP rs111321033, ExAC rs111321033, TOPMed rs111321033, CADD 17.00, PolyPhen-2 0.00, Uncertain significance
- V9L (p.Val9Leu), rs111321033, ClinGen CA343026972, ClinVar RCV002227318, 1000Genomes rs111321033, CADD 18.80, PolyPhen-2 0.00, Uncertain significance, not provided
- V10E (p.Val10Glu), ExAC rs773179413, TOPMed rs773179413, gnomAD rs773179413
- V10G (p.Val10Gly), ExAC rs773179413, TOPMed rs773179413, gnomAD rs773179413
- V10L (p.Val10Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E11D (p.Glu11Asp), rs41273533, ClinGen CA1184269, ClinVar RCV000756695, ClinVar RCV001098793, CADD 7.62, PolyPhen-2 0.00, Conflicting interpretations, Pyropoikilocytosis, hereditary; Elliptocytosis 2; Hereditary spherocytosis type
- E11G (p.Glu11Gly), rs769982359, ClinGen CA1184270, ClinVar RCV002013930, ClinVar RCV004046674, CADD 24.40, PolyPhen-2 0.07, Conflicting interpretations, not provided; not specified
- S12G (p.Ser12Gly), 1000Genomes rs141813438, gnomAD rs141813438, CADD 25.10, PolyPhen-2 0.52
- S12I (p.Ser12Ile), gnomAD rs1655097890, CADD 24.10, PolyPhen-2 0.90
- S12N (p.Ser12Asn), gnomAD rs1655097890, CADD 19.20, PolyPhen-2 0.44
- S12R (p.Ser12Arg), ExAC rs776887942, gnomAD rs776887942, CADD 17.10, PolyPhen-2 0.14
- S13R (p.Ser13Arg), ExAC rs771821343, gnomAD rs771821343, CADD 16.30, PolyPhen-2 0.29
- G14R (p.Gly14Arg), ExAC rs778856242, TOPMed rs778856242, gnomAD rs778856242, CADD 25.10, PolyPhen-2 0.97, Uncertain significance, not provided
- K16M (p.Lys16Met), rs201634881, ClinGen CA1184264, cosmic curated COSV10746, ClinVar RCV001098790, CADD 26.00, PolyPhen-2 0.84, Conflicting interpretations, Hereditary spherocytosis type 3; not provided; Elliptocytosis 2
- V17A (p.Val17Ala), ExAC rs748768867, gnomAD rs748768867, CADD 24.20, PolyPhen-2 0.24
- V17I (p.Val17Ile), gnomAD rs1370792125
- L18S (p.Leu18Ser), ExAC rs777146280, TOPMed rs777146280, gnomAD rs777146280, CADD 28.50, PolyPhen-2 0.99
- L18W (p.Leu18Trp), ExAC rs777146280, TOPMed rs777146280, gnomAD rs777146280, CADD 28.90, PolyPhen-2 1.00
- T20R (p.Thr20Arg), TOPMed rs1655094628, CADD 24.60, PolyPhen-2 0.68
- A21E (p.Ala21Glu), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63756, Variant assessed as somatic; moderate impact.
- A21G (p.Ala21Gly), ExAC rs752380355, TOPMed rs752380355, gnomAD rs752380355, CADD 24.40, PolyPhen-2 0.75, Uncertain significance, not provided
- E23A (p.Glu23Ala), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63757, Variant assessed as somatic; moderate impact.
- E23Q (p.Glu23Gln), NCI-TCGA Cosmic COSV1009, NCI-TCGA Cosmic COSV6375, cosmic curated COSV63755, Variant assessed as somatic; moderate impact.
- I24S (p.Ile24Ser), UniProt VAR 001324, Pathogenic, in EL2
- I24T (p.Ile24Thr), gnomAD rs1467409837, CADD 27.80, PolyPhen-2 1.00
- Q25H (p.Gln25His), cosmic curated COSV63751, Ensembl rs2101958909, CADD 20.40, PolyPhen-2 0.13
- E26* (p.Glu26Ter), NCI-TCGA Cosmic COSV1009, NCI-TCGA Cosmic COSV6375, cosmic curated COSV63757, Variant assessed as somatic; high impact.
- E26K (p.Glu26Lys), rs767319344, NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, NCI-TCGA Cosmic COSV6375, Variant assessed as somatic; moderate impact.
- E26Q (p.Glu26Gln), ExAC rs767319344, gnomAD rs767319344
- R28C (p.Arg28Cys), rs121918642, ClinGen CA122758, NCI-TCGA Cosmic COSV6375, cosmic curated COSV63752, CADD 27.20, PolyPhen-2 1.00, Pathogenic/Likely pathogenic, SPTA1-related disorder; not provided; Elliptocytosis 2
- R28H (p.Arg28His), rs121918641, ClinGen CA122759, NCI-TCGA Cosmic COSV1009, NCI-TCGA Cosmic COSV6374, CADD 27.40, PolyPhen-2 0.99, Pathogenic/Likely pathogenic, Prenatal anemia; not provided; Hereditary spherocytosis type 3
- R28L (p.Arg28Leu), rs121918641, ClinGen CA122756, NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, CADD 26.80, PolyPhen-2 0.99, Pathogenic/Likely pathogenic, not provided
- R28S (p.Arg28Ser), rs121918642, ClinGen CA122757, ClinVar RCV000013708, ClinVar RCV000013709, Pathogenic, not provided
- Q29L (p.Gln29Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q29R (p.Gln29Arg), NCI-TCGA TCGA novel, gnomAD rs1655091699, CADD 19.20, PolyPhen-2 0.01, Variant assessed as somatic; moderate impact.
- E30D (p.Glu30Asp), TOPMed rs1256377737, gnomAD rs1256377737, CADD 20.20, PolyPhen-2 0.05
- E30G (p.Glu30Gly), ESP rs367992717, ExAC rs367992717, gnomAD rs367992717
- E30K (p.Glu30Lys), rs766853527, NCI-TCGA Cosmic COSV6374, cosmic curated COSV63749, ExAC rs766853527, CADD 22.70, PolyPhen-2 0.01, Variant assessed as somatic; moderate impact.
- V31A (p.Val31Ala), rs773826036, ClinGen CA1184255, cosmic curated COSV63752, ClinVar RCV003138695, CADD 27.90, PolyPhen-2 0.99, Uncertain significance, not provided
- V31L (p.Val31Leu), rs993458519, TOPMed rs993458519, gnomAD rs993458519, Variant assessed as somatic; moderate impact., in EL2
- V31M (p.Val31Met), TOPMed rs993458519, gnomAD rs993458519, CADD 26.50, PolyPhen-2 0.99
- L32F (p.Leu32Phe), rs1221979324, NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, Variant assessed as somatic; moderate impact.
- T33I (p.Thr33Ile), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63759, Variant assessed as somatic; moderate impact.
- T33N (p.Thr33Asn), ExAC rs765278715, gnomAD rs765278715, CADD 6.64, PolyPhen-2 0.00
- T33S (p.Thr33Ser), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63752, Variant assessed as somatic; moderate impact.
- R34P (p.Arg34Pro), rs567686069, ClinGen CA343026807, ClinVar RCV001001220, ClinVar RCV001784536, Conflicting interpretations, not provided; not specified
- R34Q (p.Arg34Gln), cosmic curated COSV63748, 1000Genomes rs567686069, ExAC rs567686069, TOPMed rs567686069, CADD 23.60, PolyPhen-2 0.10, Likely pathogenic, in EL2
- R34W (p.Arg34Trp), rs201568233, NCI-TCGA Cosmic COSV6375, cosmic curated COSV63752, UniProt VAR 001330, CADD 27.50, PolyPhen-2 0.98, Pathogenic, in EL2
- Y35H (p.Tyr35His), gnomAD rs1394253367
- S37C (p.Ser37Cys), ExAC rs776791339, gnomAD rs776791339, CADD 23.70, PolyPhen-2 0.12
- S37N (p.Ser37Asn), cosmic curated COSV10746, TOPMed rs1188198052, gnomAD rs1188198052, CADD 15.10, PolyPhen-2 0.00
- F38L (p.Phe38Leu), 1000Genomes rs370472299, CADD 23.40, PolyPhen-2 0.32, Uncertain significance, not provided
- F38S (p.Phe38Ser), rs1366921505, ClinGen CA343026779, ClinVar RCV003491555, TOPMed rs1366921505, CADD 31.00, PolyPhen-2 0.99, Uncertain significance, not provided
- E40Q (p.Glu40Gln), TOPMed rs1166227316, gnomAD rs1166227316, CADD 18.60, PolyPhen-2 0.01
- R41P (p.Arg41Pro), TOPMed rs778903567, gnomAD rs778903567, CADD 18.50, PolyPhen-2 0.17, Uncertain significance, in EL2
- R41Q (p.Arg41Gln), rs778903567, ClinGen CA31272556, cosmic curated COSV63754, ClinVar RCV001508008, CADD 16.70, PolyPhen-2 0.00, Conflicting interpretations, not provided
- R41W (p.Arg41Trp), rs121918640, ClinGen CA122755, cosmic curated COSV63754, ClinVar RCV000013706, CADD 24.80, PolyPhen-2 0.52, Pathogenic, Elliptocytosis 2
- V42A (p.Val42Ala), TOPMed rs1382500308, gnomAD rs1382500308, CADD 22.40, PolyPhen-2 0.03
- V42I (p.Val42Ile), ExAC rs770828837, gnomAD rs770828837, CADD 21.40, PolyPhen-2 0.13
- A43T (p.Ala43Thr), rs933454103, NCI-TCGA Cosmic COSV6375, cosmic curated COSV63758, TOPMed rs933454103, Variant assessed as somatic; moderate impact.
- E44* (p.Glu44Ter), TOPMed rs1655083877, CADD 38.00
- E44D (p.Glu44Asp), ESP rs377396196, ExAC rs377396196, TOPMed rs377396196, gnomAD rs377396196, CADD 16.70, PolyPhen-2 0.01
- E44G (p.Glu44Gly), rs2525389932, ClinGen CA343026742, ClinVar RCV003736438, Uncertain significance, not provided
- R45G (p.Arg45Gly), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63751, Variant assessed as somatic; moderate impact., in EL2
- R45K (p.Arg45Lys), rs374697328, NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, ESP rs374697328, CADD 22.40, PolyPhen-2 0.11, Uncertain significance, not specified
- R45M (p.Arg45Met), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, CADD 26.70, PolyPhen-2 0.94, Variant assessed as somatic; moderate impact., in EL2
- R45S (p.Arg45Ser), rs121918637, ClinGen CA122752, ClinVar RCV000013702, ClinVar RCV000013703, Pathogenic, Elliptocytosis 2; Pyropoikilocytosis, hereditary
- R45T (p.Arg45Thr), rs374697328, ClinGen CA343026736, ClinVar RCV003132655, UniProt VAR 001333, Conflicting interpretations, not provided
- G46C (p.Gly46Cys), rs1655082524, ClinGen CA343026731, ClinVar RCV003665831, gnomAD rs1655082524, CADD 25.90, PolyPhen-2 0.95, Uncertain significance, not provided
- G46V (p.Gly46Val), rs121918638, ClinGen CA122753, ClinVar RCV000013704, ClinVar RCV006461145, CADD 23.20, PolyPhen-2 0.84, Conflicting interpretations, not provided; Elliptocytosis 2
- K48N (p.Lys48Asn), ExAC rs754692537, TOPMed rs754692537, gnomAD rs754692537, CADD 24.30, PolyPhen-2 0.98
- K48R (p.Lys48Arg), rs121918644, ClinGen CA122761, cosmic curated COSV63753, ClinVar RCV000013716, CADD 23.00, PolyPhen-2 0.20, Uncertain significance, not provided
- L49F (p.Leu49Phe), rs121918639, ClinGen CA122754, ClinVar RCV000013705, ClinVar RCV001004905, Uncertain significance, Elliptocytosis 2; Hereditary spherocytosis type 2
- L49H (p.Leu49His), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, Variant assessed as somatic; moderate impact., in EL2
- E50K (p.Glu50Lys), cosmic curated COSV10651, Ensembl rs2101958351, Uncertain significance, not specified
- D51N (p.Asp51Asn), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, Variant assessed as somatic; moderate impact.
- D51Y (p.Asp51Tyr), NCI-TCGA Cosmic COSV1009, Variant assessed as somatic; moderate impact.
- S52F (p.Ser52Phe), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, CADD 27.00, PolyPhen-2 0.99, Uncertain significance, not specified
- H54Q (p.His54Gln), TOPMed rs1655080981
- Q56H (p.Gln56His), cosmic curated COSV63752, Ensembl rs1655080420
- V57A (p.Val57Ala), NCI-TCGA Cosmic COSV6376, cosmic curated COSV63761, CADD 22.60, PolyPhen-2 0.41, Variant assessed as somatic; moderate impact.
- F58L (p.Phe58Leu), 1000Genomes rs190704778, ESP rs190704778, ExAC rs190704778, TOPMed rs190704778, CADD 25.30, PolyPhen-2 1.00, Benign
- K59E (p.Lys59Glu), TOPMed rs1218579692, gnomAD rs1218579692, CADD 23.00, PolyPhen-2 0.15
- R60* (p.Arg60Ter), rs373695294, ClinGen CA1184242, cosmic curated COSV63752, ClinVar RCV001508007, CADD 36.00, Pathogenic
- R60P (p.Arg60Pro), rs750863150, ClinGen CA343026555, ClinVar RCV003138687, ExAC rs750863150, Uncertain significance, not provided
- R60Q (p.Arg60Gln), rs750863150, NCI-TCGA Cosmic COSV6374, cosmic curated COSV63748, ExAC rs750863150, CADD 25.10, PolyPhen-2 1.00, Uncertain significance, Hereditary spherocytosis type 3
- D61E (p.Asp61Glu), 1000Genomes rs539667133, ExAC rs539667133, gnomAD rs539667133, CADD 23.60, PolyPhen-2 0.86, Likely benign, not provided
- D61Y (p.Asp61Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A62T (p.Ala62Thr), TOPMed rs1396574054, gnomAD rs1396574054, CADD 26.50, PolyPhen-2 0.87
- D63V (p.Asp63Val), Ensembl rs2101958128, CADD 28.70, PolyPhen-2 0.99
- D64E (p.Asp64Glu), rs200860772, ClinGen CA1184237, ClinVar RCV000269779, ClinVar RCV000327229, CADD 16.30, PolyPhen-2 0.00, Conflicting interpretations, Pyropoikilocytosis, hereditary; not provided; Hereditary spherocytosis type 3
- D64V (p.Asp64Val), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, Variant assessed as somatic; moderate impact.
- D64Y (p.Asp64Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G66E (p.Gly66Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G66R (p.Gly66Arg), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63758, Variant assessed as somatic; moderate impact.
- K67E (p.Lys67Glu), rs1273701490, ClinGen CA343025606, ClinVar RCV003138676, gnomAD rs1273701490, CADD 23.10, Uncertain significance, not provided
- K67N (p.Lys67Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- W68C (p.Trp68Cys), rs1655076780, ClinGen CA343025581, ClinVar RCV001100510, ClinVar RCV001100511, CADD 28.70, PolyPhen-2 1.00, Uncertain significance, Hereditary spherocytosis type 3; Elliptocytosis 2; Pyropoikilocytosis, hereditar
- W68R (p.Trp68Arg), rs2101958016, ClinGen CA343025591, ClinVar RCV001509089, Ensembl rs2101958016, Uncertain significance, not provided
- I69T (p.Ile69Thr), 1000Genomes rs41273531, ExAC rs41273531, TOPMed rs41273531, gnomAD rs41273531, CADD 26.70, PolyPhen-2 0.99
- I69V (p.Ile69Val), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, Variant assessed as somatic; moderate impact.
- M70I (p.Met70Ile), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63756, Variant assessed as somatic; moderate impact.
- M70K (p.Met70Lys), TOPMed rs1469938477, gnomAD rs1469938477, Uncertain significance
- M70R (p.Met70Arg), rs1469938477, ClinGen CA343025539, ClinVar RCV001509088, TOPMed rs1469938477, CADD 18.10, PolyPhen-2 0.04, Conflicting interpretations, not provided
- E71D (p.Glu71Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K72E (p.Lys72Glu), ExAC rs770613744, TOPMed rs770613744, gnomAD rs770613744, CADD 26.40, PolyPhen-2 1.00
- K72T (p.Lys72Thr), TOPMed rs1655075752
- V73F (p.Val73Phe), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, Variant assessed as somatic; moderate impact.
- N74S (p.Asn74Ser), ExAC rs762849672, TOPMed rs762849672, gnomAD rs762849672, CADD 22.90, PolyPhen-2 0.00
- I75T (p.Ile75Thr), rs146993090, ClinGen CA1184231, ClinVar RCV000266135, ClinVar RCV000323519, CADD 12.00, PolyPhen-2 0.03, Conflicting interpretations, not provided; Elliptocytosis 2; Pyropoikilocytosis, hereditary
- L76V (p.Leu76Val), NCI-TCGA Cosmic COSV6374, NCI-TCGA Cosmic COSV6375, cosmic curated COSV63754, Variant assessed as somatic; moderate impact.
- T77I (p.Thr77Ile), ESP rs372828197, ExAC rs372828197, TOPMed rs372828197, gnomAD rs372828197, CADD 0.03, PolyPhen-2 0.08, Conflicting interpretations, not specified; not provided
- T77N (p.Thr77Asn), ESP rs372828197, ExAC rs372828197, TOPMed rs372828197, gnomAD rs372828197, Conflicting interpretations, not specified; not provided
- D78N (p.Asp78Asn), NCI-TCGA Cosmic COSV6374, cosmic curated COSV63749, NCI-TCGA Cosmic COSV6375, CADD 21.20, PolyPhen-2 0.32, Uncertain significance, not provided
- D78Y (p.Asp78Tyr), cosmic curated COSV63750, Ensembl rs1655074304, CADD 24.30, PolyPhen-2 0.99, Uncertain significance, not provided
- S80I (p.Ser80Ile), rs186235809, 1000Genomes rs186235809, ExAC rs186235809, TOPMed rs186235809, CADD 22.80, PolyPhen-2 0.78, Variant assessed as somatic; moderate impact.
- S80N (p.Ser80Asn), cosmic curated COSV10529, 1000Genomes rs186235809, ExAC rs186235809, TOPMed rs186235809, CADD 13.30, PolyPhen-2 0.01
- S80R (p.Ser80Arg), cosmic curated COSV63749, ExAC rs746617648, gnomAD rs746617648
- Y81C (p.Tyr81Cys), TOPMed rs1448936100
- Y81H (p.Tyr81His), ExAC rs779796618, TOPMed rs779796618, gnomAD rs779796618, CADD 23.60, PolyPhen-2 0.88
- E82* (p.Glu82Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E82D (p.Glu82Asp), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63752, Variant assessed as somatic; moderate impact.
- E82K (p.Glu82Lys), gnomAD rs1354772766, CADD 17.50, PolyPhen-2 0.00
- P84T (p.Pro84Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T85I (p.Thr85Ile), TOPMed rs1290835563, gnomAD rs1290835563, CADD 23.70, PolyPhen-2 0.80, Uncertain significance, not provided
- T85N (p.Thr85Asn), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63752, Variant assessed as somatic; moderate impact.
- T85S (p.Thr85Ser), TOPMed rs1290835563, gnomAD rs1290835563, CADD 18.40, PolyPhen-2 0.02
- N86I (p.Asn86Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I87T (p.Ile87Thr), ExAC rs757763837, TOPMed rs757763837, gnomAD rs757763837, CADD 25.10, PolyPhen-2 0.92
- I87V (p.Ile87Val), ESP rs369020363, ExAC rs369020363, TOPMed rs369020363, gnomAD rs369020363, CADD 23.30, PolyPhen-2 0.24, Uncertain significance, not specified
- Q88* (p.Gln88Ter), rs2101957676, ClinGen CA343025228, ClinVar RCV001783802, Ensembl rs2101957676, Likely pathogenic
- Q88R (p.Gln88Arg), Ensembl rs2101957662
- G89=, rs973802070, NCI-TCGA Cosmic COSV6375, Variant assessed as somatic; low impact.
- G89E (p.Gly89Glu), rs1557997384, ClinGen CA343025011, cosmic curated COSV63758, ClinVar RCV004465344, CADD 23.00, PolyPhen-2 0.87, Uncertain significance, not specified
- G89R (p.Gly89Arg), gnomAD rs1424359336, CADD 32.00, PolyPhen-2 0.91
- G89W (p.Gly89Trp), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63753, Variant assessed as somatic; moderate impact.
- K90N (p.Lys90Asn), TOPMed rs1654955153, gnomAD rs1654955153, CADD 23.20, PolyPhen-2 1.00
- Y91H (p.Tyr91His), Ensembl rs1654954982
- Q92R (p.Gln92Arg), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, TOPMed rs1654954842, CADD 16.40, PolyPhen-2 0.03, Variant assessed as somatic; moderate impact.
- K93N (p.Lys93Asn), TOPMed rs1490821655
- K93R (p.Lys93Arg), rs1167438530, NCI-TCGA Cosmic COSV6375, cosmic curated COSV63751, gnomAD rs1167438530, CADD 24.50, PolyPhen-2 0.68, Variant assessed as somatic; moderate impact.
- K93T (p.Lys93Thr), NCI-TCGA Cosmic COSV6375, Variant assessed as somatic; moderate impact.
- H94Q (p.His94Gln), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, ExAC rs746161030, gnomAD rs746161030, Variant assessed as somatic; moderate impact.
- H94Y (p.His94Tyr), gnomAD rs1474509932, CADD 23.30, PolyPhen-2 0.42
- Q95E (p.Gln95Glu), NCI-TCGA Cosmic COSV6375, Variant assessed as somatic; moderate impact.
- Q95H (p.Gln95His), TOPMed rs1654953959, CADD 5.01, PolyPhen-2 0.02
- Q95K (p.Gln95Lys), NCI-TCGA Cosmic COSV6375, Variant assessed as somatic; moderate impact.
- S96T (p.Ser96Thr), ExAC rs779242030, gnomAD rs779242030, CADD 5.42, PolyPhen-2 0.00
- L97F (p.Leu97Phe), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63755, Variant assessed as somatic; moderate impact.
- E98D (p.Glu98Asp), NCI-TCGA Cosmic COSV6374, cosmic curated COSV63749, Variant assessed as somatic; moderate impact.
- A99E (p.Ala99Glu), NCI-TCGA Cosmic COSV6375, cosmic curated COSV63751, Variant assessed as somatic; moderate impact.
- E100* (p.Glu100Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E100Q (p.Glu100Gln), TOPMed rs1222514583, CADD 24.20, PolyPhen-2 0.99
- V101M (p.Val101Met), Ensembl rs1654953425
- Q102* (p.Gln102Ter), gnomAD rs1467867283, CADD 34.00
- Q102H (p.Gln102His), Ensembl rs1173670907
- Q102P (p.Gln102Pro), TOPMed rs1267545224, CADD 22.40, PolyPhen-2 0.61
- S105* (p.Ser105Ter), Ensembl rs1479210455
- S105L (p.Ser105Leu), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, Variant assessed as somatic; moderate impact.
- R106G (p.Arg106Gly), gnomAD rs1321388973, CADD 6.34, PolyPhen-2 0.00
- R106T (p.Arg106Thr), TOPMed rs961147463, gnomAD rs961147463, CADD 0.42, PolyPhen-2 0.04
- L107F (p.Leu107Phe), rs572059809, ClinGen CA1184200, ClinVar RCV004309494, 1000Genomes rs572059809, CADD 13.10, PolyPhen-2 0.04, Uncertain significance, not specified
- L107I (p.Leu107Ile), 1000Genomes rs572059809, ExAC rs572059809, gnomAD rs572059809, CADD 5.89, PolyPhen-2 0.00, Uncertain significance
- M108I (p.Met108Ile), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10093, CADD 0.44, PolyPhen-2 0.00, Likely benign, not specified
- M108T (p.Met108Thr), gnomAD rs1318545144, CADD 21.60, PolyPhen-2 0.06
Public SPTA1 analysis runs
- SPTA1 analysis run — SPTA1 (4,239 variants) — completed 2026-08-21