SRSF2 (Q01130) variants and mutations
SRSF2 (also known as Q01130) is a human protein-coding gene encoding a serine/arginine-rich splicing factor 2 protein. It helps select splice sites during pre-mRNA processing and coordinates multiple stages of RNA maturation. Recurrent P95 hotspot mutations change RNA-binding preferences and are common in myelodysplastic syndromes, chronic myelomonocytic leukemia, and AML. This analysis covers 691 SRSF2 variants and mutations. Of these, 60% have computational variant effect predictions. Disease context includes acute myeloid leukemia, myelodysplastic syndrome, and hemorrhagic disease. Example SRSF2 variants include M1?, S2R, and S2T.
Variant analysis overview
- Gene: SRSF2
- Protein: Q01130
- UniProt accession: Q01130
- Organism: Homo sapiens
- Variants analyzed: 691
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 423 unspecified-consequence records; 1 stop retained variant; 158 synonymous variants; 12 in-frame deletions; 6 stop-gained variants; 7 frameshift variants; 78 missense variants; 1 incomplete terminal codon variant; 2 splice-region variants; 2 in-frame insertions; 1 protein altering variant
- Prediction scores: 418 variants have prediction scores (60% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: acute myeloid leukemia, myelodysplastic syndrome, hemorrhagic disease, Sepsis, chronic myelomonocytic leukemia, lymphoid neoplasm, Absence of circulating granulocytes, neoplasm, myeloid leukemia, hematologic disorder, hematopoietic and lymphoid system neoplasm, purpura.
Protein structure and variant hotspots
- Protein features: 1 domains; 13 post-translational modification sites.
- Structural context: 159 variants have structural context.
- PTM context: 54 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable SRSF2 variants
Examples include M1?, S2R, S2T, S2S, S2N, S2I, S2G, Y3H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, NCI-TCGA Cosmic COSV5797, cosmic curated COSV57975, Variant assessed as somatic; high impact.
- S2R (p.Ser2Arg), NCI-TCGA TCGA novel, REVEL 0.17, CADD 23.00, Variant assessed as somatic; moderate impact.
- S2T (p.Ser2Thr), Ensembl rs2077546003
- S2S (p.Ser2Ser), rs1161360426, gnomAD 17-76737155-G-A, CADD 10.80
- S2N (p.Ser2Asn), gnomAD 17-76737156-C-T, REVEL 0.08, CADD 23.20
- S2I (p.Ser2Ile), gnomAD 17-76737156-C-A, REVEL 0.29, CADD 26.00
- S2G (p.Ser2Gly), gnomAD 17-76737157-T-C, REVEL 0.17, CADD 26.20
- Y3H (p.Tyr3His), gnomAD rs1474816451, REVEL 0.26, CADD 28.40
- Y3* (p.Tyr3Ter), gnomAD 17-76737152-G-T, CADD 40.00
- Y3Y (p.Tyr3Tyr), rs1373611272, gnomAD 17-76737152-G-A, CADD 12.60
- Y3C (p.Tyr3Cys), gnomAD 17-76737153-T-C, REVEL 0.29, CADD 23.60
- G4D (p.Gly4Asp), cosmic curated COSV57973
- G4G (p.Gly4Gly), rs760991597, gnomAD 17-76737149-G-T, CADD 9.63
- G4V (p.Gly4Val), gnomAD 17-76737150-C-A, REVEL 0.30, CADD 24.50
- G4S (p.Gly4Ser), gnomAD 17-76737151-C-T, REVEL 0.22, CADD 21.30
- G4C (p.Gly4Cys), gnomAD 17-76737151-C-A, REVEL 0.28, CADD 25.50
- R5R (p.Arg5Arg), rs775513335, gnomAD 17-76737146-G-A, CADD 15.10
- R5H (p.Arg5His), gnomAD 17-76737147-C-T, REVEL 0.39, CADD 26.30
- R5L (p.Arg5Leu), gnomAD 17-76737147-C-A, REVEL 0.61, CADD 30.00
- R5C (p.Arg5Cys), gnomAD 17-76737148-G-A, REVEL 0.38, CADD 27.30
- R5S (p.Arg5Ser), gnomAD 17-76737148-G-T, REVEL 0.31, CADD 29.00
- P6P (p.Pro6Pro), gnomAD 17-76737143-G-T, CADD 15.00
- P6H (p.Pro6His), gnomAD 17-76737144-G-T, REVEL 0.55, CADD 31.00
- P6L (p.Pro6Leu), gnomAD 17-76737144-G-A, REVEL 0.50, CADD 31.00
- P6S (p.Pro6Ser), gnomAD 17-76737145-G-A, REVEL 0.37, CADD 24.60
- P6A (p.Pro6Ala), gnomAD 17-76737145-G-C, REVEL 0.29, CADD 22.90
- P7L (p.Pro7Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P7P (p.Pro7Pro), gnomAD 17-76737140-A-G, CADD 13.90
- P8L (p.Pro8Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P8S (p.Pro8Ser), cosmic curated COSV10520
- P8P (p.Pro8Pro), gnomAD 17-76737137-G-T, CADD 15.20
- D9N (p.Asp9Asn), cosmic curated COSV57973, REVEL 0.17, CADD 22.30
- D9D (p.Asp9Asp), gnomAD 17-76737134-A-G, CADD 14.20
- D9M (p.Asp9Met), gnomAD 17-76737136-CG-C, CADD 29.50
- D9Y (p.Asp9Tyr), gnomAD 17-76737136-C-A, REVEL 0.60, CADD 25.70
- V10A (p.Val10Ala), NCI-TCGA TCGA novel, REVEL 0.50, CADD 29.20, Variant assessed as somatic; moderate impact.
- V10V (p.Val10Val), gnomAD 17-76737131-C-A, CADD 14.40
- V10M (p.Val10Met), gnomAD 17-76737133-C-T, REVEL 0.31, CADD 27.50
- E11E (p.Glu11Glu), rs1452226582, gnomAD 17-76737128-C-T, CADD 14.70
- E11D (p.Glu11Asp), gnomAD 17-76737128-C-A, REVEL 0.26, CADD 21.90
- E11G (p.Glu11Gly), gnomAD 17-76737129-T-C, REVEL 0.26, CADD 24.10
- E11* (p.Glu11Ter), gnomAD 17-76737130-C-A, CADD 39.00
- G12D (p.Gly12Asp), cosmic curated COSV57976
- G12S (p.Gly12Ser), Ensembl rs2077544142
- G12G (p.Gly12Gly), rs1598434712, gnomAD 17-76737125-A-G, CADD 15.20
- G12V (p.Gly12Val), gnomAD 17-76737126-C-A, REVEL 0.62, CADD 28.10
- M13I (p.Met13Ile), cosmic curated COSV57976, gnomAD rs1292696054
- T14T (p.Thr14Thr), rs546284289, gnomAD 17-76737119-G-C, CADD 14.80
- S15F (p.Ser15Phe), cosmic curated COSV57972
- S15S (p.Ser15Ser), rs17849462, gnomAD 17-76737116-G-A, CADD 14.30
- L16F (p.Leu16Phe), cosmic curated COSV10520
- L16L (p.Leu16Leu), rs1289391142, gnomAD 17-76737113-G-C, CADD 13.50
- K17K (p.Lys17Lys), gnomAD 17-76737110-C-T, CADD 14.90
- V18L (p.Val18Leu), TOPMed rs1237040767, REVEL 0.47, CADD 27.10
- V18V (p.Val18Val), rs1230550019, gnomAD 17-76737107-C-T, CADD 14.60
- D19G (p.Asp19Gly), cosmic curated COSV10590
- D19Y (p.Asp19Tyr), cosmic curated COSV10590
- D19D (p.Asp19Asp), rs778139770, gnomAD 17-76737104-G-A, CADD 14.40
- N20N (p.Asn20Asn), rs2077542102, gnomAD 17-76737101-G-A, CADD 14.50
- L21L (p.Leu21Leu), rs756403208, gnomAD 17-76737098-C-T, CADD 14.10
- L21P (p.Leu21Pro), gnomAD 17-76737099-A-G, REVEL 0.90, CADD 32.00
- L21R (p.Leu21Arg), gnomAD 17-76737099-A-C, REVEL 0.91, CADD 32.00
- L21V (p.Leu21Val), gnomAD 17-76737100-G-C, REVEL 0.80, CADD 24.90
- T22A (p.Thr22Ala), cosmic curated COSV57971
- T22T (p.Thr22Thr), gnomAD 17-76737095-G-T, CADD 14.00
- Y23H (p.Tyr23His), cosmic curated COSV10740
- Y23N (p.Tyr23Asn), cosmic curated COSV10740, REVEL 0.55, CADD 23.50
- R24R (p.Arg24Arg), rs1383376190, gnomAD 17-76737089-G-A, CADD 15.00
- T25S (p.Thr25Ser), cosmic curated COSV57971
- T25T (p.Thr25Thr), rs61742084, gnomAD 17-76737086-G-A, CADD 14.30
- S26* (p.Ser26Ter), NCI-TCGA Cosmic COSV5797, cosmic curated COSV57974, Variant assessed as somatic; high impact.
- S26L (p.Ser26Leu), gnomAD rs1568027382, REVEL 0.63, CADD 32.00
- S26A (p.Ser26Ala), gnomAD 17-76737085-A-C, REVEL 0.38, CADD 24.70
- P27P (p.Pro27Pro), rs140957080, gnomAD 17-76737080-G-A, CADD 13.90
- P27L (p.Pro27Leu), gnomAD 17-76737081-G-A, REVEL 0.64, CADD 24.20
- D28D (p.Asp28Asp), rs757990285, gnomAD 17-76737077-G-A, CADD 14.90
- T29M (p.Thr29Met), Ensembl rs2077540071, REVEL 0.48, CADD 28.90
- T29T (p.Thr29Thr), gnomAD 17-76737074-C-A, CADD 9.67
- L30L (p.Leu30Leu), gnomAD 17-76737071-C-T, CADD 11.80
- R31R (p.Arg31Arg), gnomAD 17-76737068-C-T, CADD 16.00
- R32R (p.Arg32Arg), rs372496093, gnomAD 17-76737065-G-A, CADD 15.60
- V33V (p.Val33Val), rs1031504488, gnomAD 17-76737062-G-A, CADD 12.90
- F34F (p.Phe34Phe), rs2077539634, gnomAD 17-76737059-G-A, CADD 15.40
- E35K (p.Glu35Lys), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, Variant assessed as somatic; moderate impact.
- E35Q (p.Glu35Gln), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, Variant assessed as somatic; moderate impact.
- E35G (p.Glu35Gly), gnomAD 17-76737057-T-C, REVEL 0.42, CADD 32.00
- K36N (p.Lys36Asn), gnomAD rs1471478638, REVEL 0.21, CADD 27.00
- K36T (p.Lys36Thr), ExAC rs757286065, gnomAD rs757286065, REVEL 0.47, CADD 31.00
- Y37C (p.Tyr37Cys), cosmic curated COSV10610, NCI-TCGA TCGA novel, REVEL 0.79, CADD 32.00, Variant assessed as somatic; moderate impact.
- Y37Y (p.Tyr37Tyr), rs575538276, gnomAD 17-76737050-G-A, CADD 14.00
- Y37N (p.Tyr37Asn), gnomAD 17-76737052-A-T, REVEL 0.93, CADD 32.00
- G38G (p.Gly38Gly), rs763988734, gnomAD 17-76737047-C-A, CADD 14.30
- R39R (p.Arg39Arg), rs999131144, gnomAD 17-76737044-G-A, CADD 16.30
- R39G (p.Arg39Gly), gnomAD 17-76737046-G-C, REVEL 0.33, CADD 25.50
- V40V (p.Val40Val), gnomAD 17-76737041-G-A, CADD 11.60
- G41G (p.Gly41Gly), rs61742139, gnomAD 17-76737038-G-C, CADD 16.00
- D42A (p.Asp42Ala), Ensembl rs2143949348
- D42D (p.Asp42Asp), rs1211837574, gnomAD 17-76737035-G-A, CADD 15.30
- V43V (p.Val43Val), rs2077538445, gnomAD 17-76737032-C-T, CADD 15.40
- Y44H (p.Tyr44His), cosmic curated COSV57974, Ensembl rs1782475642, REVEL 0.38, CADD 32.00
- I45V (p.Ile45Val), ExAC rs775840051, gnomAD rs775840051, REVEL 0.20, CADD 27.40
- I45I (p.Ile45Ile), rs1269318968, gnomAD 17-76737026-G-A, CADD 15.60
- P46Q (p.Pro46Gln), cosmic curated COSV10033, REVEL 0.58, CADD 32.00
- P46P (p.Pro46Pro), gnomAD 17-76737023-C-T, CADD 16.30
- R47L (p.Arg47Leu), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, NCI-TCGA Cosmic COSV5797, Variant assessed as somatic; moderate impact.
- R47Q (p.Arg47Gln), cosmic curated COSV57975
- R47P (p.Arg47Pro), gnomAD 17-76737017-GTCCC, CADD 33.00
- R47R (p.Arg47Arg), gnomAD 17-76737020-C-T, CADD 16.30
- D48E (p.Asp48Glu), 1000Genomes rs237057, ESP rs237057, ExAC rs237057, TOPMed rs237057, Benign
- D48G (p.Asp48Gly), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, Variant assessed as somatic; moderate impact.
- D48D (p.Asp48Asp), rs237057, gnomAD 17-76737017-G-A, CADD 14.70
- R49R (p.Arg49Arg), rs759702439, gnomAD 17-76737014-G-C, CADD 16.40
- Y50L (p.Tyr50Leu), gnomAD 17-76736991-AAGCC, CADD 33.00
- Y50Y (p.Tyr50Tyr), rs2077536958, gnomAD 17-76737011-G-A, CADD 14.50
- T51A (p.Thr51Ala), gnomAD rs2077536769, REVEL 0.76, CADD 28.70
- T51I (p.Thr51Ile), cosmic curated COSV57973
- T51T (p.Thr51Thr), rs774394478, gnomAD 17-76737008-G-A, CADD 15.80
- T51S (p.Thr51Ser), gnomAD 17-76737010-T-A, REVEL 0.55, CADD 24.50
- K52N (p.Lys52Asn), NCI-TCGA Cosmic COSV5797, cosmic curated COSV57975, REVEL 0.19, CADD 22.60, Variant assessed as somatic; moderate impact.
- K52K (p.Lys52Lys), rs770956483, gnomAD 17-76737005-C-T, CADD 15.10
- E53K (p.Glu53Lys), NCI-TCGA Cosmic COSV5797, cosmic curated COSV57971, Variant assessed as somatic; moderate impact.
- E53E (p.Glu53Glu), gnomAD 17-76737002-C-T, CADD 15.10
- S54F (p.Ser54Phe), cosmic curated COSV57971, REVEL 0.79, CADD 32.00
- S54S (p.Ser54Ser), rs773650940, gnomAD 17-76736999-G-C, CADD 14.40
- S54P (p.Ser54Pro), gnomAD 17-76737001-A-G, REVEL 0.58, CADD 24.20
- R55C (p.Arg55Cys), cosmic curated COSV10033
- R55H (p.Arg55His), Ensembl rs2143948615
- R55R (p.Arg55Arg), gnomAD 17-76736996-G-A, CADD 14.90
- G56G (p.Gly56Gly), rs142294903, gnomAD 17-76736993-G-A, CADD 16.30
- G56A (p.Gly56Ala), gnomAD 17-76736994-C-G, REVEL 0.92, CADD 26.90
- F57Y (p.Phe57Tyr), cosmic curated COSV57969, ESP rs369871019, ExAC rs369871019, gnomAD rs369871019, REVEL 0.62, CADD 32.00
- F57F (p.Phe57Phe), rs376379121, gnomAD 17-76736990-G-A, CADD 16.00
- A58A (p.Ala58Ala), rs779792829, gnomAD 17-76736987-G-A, CADD 15.50
- A58T (p.Ala58Thr), gnomAD 17-76736989-C-T, REVEL 0.91, CADD 26.40
- F59F (p.Phe59Phe), rs2077535432, gnomAD 17-76736984-G-A, CADD 16.20
- R61R (p.Arg61Arg), rs200354490, gnomAD 17-76736978-G-A, CADD 15.10
- F62C (p.Phe62Cys), cosmic curated COSV57975
- H63N (p.His63Asn), cosmic curated COSV10966
- H63Q (p.His63Gln), TOPMed rs1176463751, gnomAD rs1176463751, REVEL 0.24, CADD 23.70
- H63Y (p.His63Tyr), ExAC rs745477669, gnomAD rs745477669
- H63H (p.His63His), rs1176463751, gnomAD 17-76736972-G-A, CADD 13.40
- D64V (p.Asp64Val), Ensembl rs2143948134
- D64D (p.Asp64Asp), rs778600867, gnomAD 17-76736969-G-A, CADD 14.20
- K65K (p.Lys65Lys), rs1281978746, gnomAD 17-76736966-C-T, CADD 14.90
- R66C (p.Arg66Cys), cosmic curated COSV10463, TOPMed rs1427451925, gnomAD rs1427451925, REVEL 0.73, CADD 28.80
- R66R (p.Arg66Arg), rs1598434003, gnomAD 17-76736963-G-A, CADD 13.30
- D67N (p.Asp67Asn), NCI-TCGA Cosmic COSV5797, cosmic curated COSV57972, Variant assessed as somatic; moderate impact.
- D67D (p.Asp67Asp), rs756763573, gnomAD 17-76736960-G-A, CADD 15.10
- E69G (p.Glu69Gly), cosmic curated COSV10033
- E69K (p.Glu69Lys), NCI-TCGA Cosmic COSV5797, cosmic curated COSV57971, Variant assessed as somatic; moderate impact.
- E69Q (p.Glu69Gln), cosmic curated COSV57971
- E69V (p.Glu69Val), Ensembl rs2143947854
- D70D (p.Asp70Asp), gnomAD 17-76736951-G-A, CADD 15.30
- A71G (p.Ala71Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A71T (p.Ala71Thr), Ensembl rs2143947773
- A71A (p.Ala71Ala), rs1204474691, gnomAD 17-76736948-A-G, CADD 16.70
- D73D (p.Asp73Asp), rs1598433938, gnomAD 17-76736942-A-G, CADD 12.90
- A74T (p.Ala74Thr), Ensembl rs2143947652
- A74V (p.Ala74Val), gnomAD 17-76736940-G-A, REVEL 0.21, CADD 32.00
- D76G (p.Asp76Gly), cosmic curated COSV10610
- D76N (p.Asp76Asn), TOPMed rs2077533483
- D76D (p.Asp76Asp), rs766090246, gnomAD 17-76736933-G-A, CADD 14.10
- G77E (p.Gly77Glu), cosmic curated COSV57970
- G77V (p.Gly77Val), cosmic curated COSV57972
- G77W (p.Gly77Trp), cosmic curated COSV57972
- G77G (p.Gly77Gly), gnomAD 17-76736930-C-T, CADD 7.52
- G77R (p.Gly77Arg), gnomAD 17-76736932-C-G, REVEL 0.47, CADD 29.70
- A78V (p.Ala78Val), Ensembl rs2143947539
- A78A (p.Ala78Ala), rs2077533227, gnomAD 17-76736927-G-A, CADD 12.20
- V79G (p.Val79Gly), Ensembl rs2143947397
- V79M (p.Val79Met), Ensembl rs2143947437, REVEL 0.04, CADD 20.70
- V79V (p.Val79Val), rs1453859851, gnomAD 17-76736924-C-T, CADD 14.70
- D81G (p.Asp81Gly), Ensembl rs2143947233
- D81D (p.Asp81Asp), rs1000715601, gnomAD 17-76736918-G-A, CADD 14.50
- G82D (p.Gly82Asp), Ensembl rs2143947097
- G82S (p.Gly82Ser), Ensembl rs2143947157
- G82G (p.Gly82Gly), rs1315642521, gnomAD 17-76736915-G-A, CADD 14.70
- R83H (p.Arg83His), gnomAD rs1249242916, REVEL 0.67, CADD 25.10
- R83R (p.Arg83Arg), gnomAD 17-76736912-G-T, CADD 15.40
- E84K (p.Glu84Lys), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10033, Variant assessed as somatic; moderate impact.
Public SRSF2 analysis runs
- SRSF2 analysis run — SRSF2 (691 variants) — completed 2026-08-18