SF3B1 (Splicing factor 3B subunit 1) variants and mutations
SF3B1 (also known as Splicing factor 3B subunit 1) is a human protein-coding gene encoding a splicing factor 3B subunit 1 protein. It recognizes branch-point regions during spliceosome assembly and helps define correct 3-prime splice sites. Recurrent hotspot mutations alter splice-site choice and drive myelodysplastic syndromes, chronic lymphocytic leukemia, uveal melanoma, and other cancers. This analysis covers 2,363 SF3B1 variants and mutations. Of these, 30% have computational variant effect predictions. Disease context includes craniofacial microsomia, dengue disease, and neurodegenerative disease. Example SF3B1 variants include A2S, A2T, and A2V.
Variant analysis overview
- Gene: SF3B1
- Protein: Splicing factor 3B subunit 1
- UniProt accession: O75533
- Organism: Homo sapiens
- Variants analyzed: 2363
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,154 unspecified-consequence records; 1 stop lost; 1 stop retained variant; 63 missense variants; 126 synonymous variants; 2 in-frame deletions; 3 stop-gained variants; 5 frameshift variants; 4 splice-region variants; 1 in-frame insertions; 1 substitution
- Prediction scores: 717 variants have prediction scores (30% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: craniofacial microsomia, dengue disease, neurodegenerative disease, hereditary disease, colorectal carcinoma, head and neck squamous cell carcinoma, neoplasm, cardiomyopathy, hypertrophic cardiomyopathy, heart failure, cancer, prostate carcinoma.
Protein structure and variant hotspots
- Protein features: 42 post-translational modification sites.
- PTM context: 37 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, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable SF3B1 variants
Examples include A2S, A2T, A2V, K3N, I4F, I4L, I4N, I4V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2S (p.Ala2Ser), 1000Genomes rs200907946, TOPMed rs200907946, REVEL 0.14, CADD 22.90
- A2T (p.Ala2Thr), 1000Genomes rs200907946, TOPMed rs200907946
- A2V (p.Ala2Val), Ensembl rs2106031258
- K3N (p.Lys3Asn), TOPMed rs1417266098, gnomAD rs1417266098, REVEL 0.20, CADD 23.50
- I4F (p.Ile4Phe), Ensembl rs2085501052, REVEL 0.16, CADD 24.70
- I4L (p.Ile4Leu), Ensembl rs2085501052
- I4N (p.Ile4Asn), Ensembl rs1559283864
- I4V (p.Ile4Val), Ensembl rs2085501052, REVEL 0.24, CADD 22.80
- A5T (p.Ala5Thr), cosmic curated COSV59226, Ensembl rs2106031227, CADD 19.20
- A5V (p.Ala5Val), Ensembl rs2085500932, CADD 20.90
- T7I (p.Thr7Ile), rs190499887, NCI-TCGA Cosmic COSV1001, NCI-TCGA Cosmic COSV5921, cosmic curated COSV59214, REVEL 0.13, CADD 28.00, Variant assessed as somatic; moderate impact.
- T7S (p.Thr7Ser), 1000Genomes rs190499887, ExAC rs190499887, gnomAD rs190499887, REVEL 0.27, CADD 25.00
- H8L (p.His8Leu), ExAC rs763455322, gnomAD rs763455322
- H8Q (p.His8Gln), TOPMed rs1313919387, REVEL 0.13, CADD 23.30
- H8Y (p.His8Tyr), cosmic curated COSV10590, 1000Genomes rs199519570, REVEL 0.07, CADD 23.50
- E9K (p.Glu9Lys), NCI-TCGA Cosmic COSV5920, cosmic curated COSV59208, REVEL 0.07, CADD 26.40, Variant assessed as somatic; moderate impact.
- D10A (p.Asp10Ala), Ensembl rs1574552692, REVEL 0.26, CADD 24.50
- D10G (p.Asp10Gly), Ensembl rs1574552692
- D10N (p.Asp10Asn), Ensembl rs2106031196
- E12K (p.Glu12Lys), Ensembl rs2106015599
- A13T (p.Ala13Thr), Ensembl rs2106015596, REVEL 0.20, CADD 23.40
- A13V (p.Ala13Val), Ensembl rs2106015594
- I15S (p.Ile15Ser), TOPMed rs2085289315
- R16* (p.Arg16Ter), NCI-TCGA Cosmic COSV5921, NCI-TCGA Cosmic COSV5922, cosmic curated COSV59226, Ensembl rs2106015585, Variant assessed as somatic; high impact.
- R16G (p.Arg16Gly), NCI-TCGA Cosmic COSV5921, cosmic curated COSV59217, NCI-TCGA Cosmic COSV5922, Ensembl rs2106015585, Variant assessed as somatic; moderate impact.
- R16Q (p.Arg16Gln), Ensembl rs2106015582, REVEL 0.14, CADD 23.30
- E17* (p.Glu17Ter), NCI-TCGA Cosmic COSV5920, cosmic curated COSV59208, Variant assessed as somatic; high impact.
- E17D (p.Glu17Asp), TOPMed rs1297538547, gnomAD rs1297538547, REVEL 0.14, CADD 19.70
- E17G (p.Glu17Gly), TOPMed rs2085289256
- I18T (p.Ile18Thr), TOPMed rs2085289110
- I18V (p.Ile18Val), gnomAD rs1301392755, REVEL 0.19, CADD 22.10
- Q19E (p.Gln19Glu), cosmic curated COSV59212, TOPMed rs1222778757, gnomAD rs1222778757, REVEL 0.45, CADD 23.60
- Q19R (p.Gln19Arg), Ensembl rs2106015561
- G20C (p.Gly20Cys), Ensembl rs2106015557
- K22N (p.Lys22Asn), cosmic curated COSV10647, ESP rs373475459, ExAC rs373475459, TOPMed rs373475459, REVEL 0.31, CADD 23.50
- K22R (p.Lys22Arg), ExAC rs765775783, TOPMed rs765775783, gnomAD rs765775783, REVEL 0.04, CADD 22.60
- A23T (p.Ala23Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A23V (p.Ala23Val), Ensembl rs2106015536
- A24D (p.Ala24Asp), gnomAD rs1448749134
- A24V (p.Ala24Val), gnomAD rs1448749134, REVEL 0.25, CADD 23.20
- L25P (p.Leu25Pro), cosmic curated COSV59222, TOPMed rs958668455, gnomAD rs958668455, REVEL 0.37, CADD 23.40
- D26G (p.Asp26Gly), cosmic curated COSV10013, TOPMed rs1307003441
- D26H (p.Asp26His), TOPMed rs1437681259, Uncertain significance
- D26N (p.Asp26Asn), TOPMed rs1437681259, REVEL 0.25, CADD 23.10, Uncertain significance, not specified
- A28G (p.Ala28Gly), Ensembl rs2106015517
- A28T (p.Ala28Thr), Ensembl rs2106015519
- Q29E (p.Gln29Glu), Ensembl rs1348190631
- Q29P (p.Gln29Pro), ExAC rs776930930, gnomAD rs776930930, REVEL 0.34, CADD 22.70
- Q29R (p.Gln29Arg), ExAC rs776930930, gnomAD rs776930930, REVEL 0.31, CADD 22.00
- G30A (p.Gly30Ala), Ensembl rs2106015497
- V31L (p.Val31Leu), Ensembl rs2106015495
- V31M (p.Val31Met), Ensembl rs2106015495
- G32D (p.Gly32Asp), Ensembl rs2106015492
- G32V (p.Gly32Val), Ensembl rs2106015492
- D34N (p.Asp34Asn), rs890785458, NCI-TCGA Cosmic COSV5921, cosmic curated COSV59212, TOPMed rs890785458, REVEL 0.20, CADD 22.50, Variant assessed as somatic; moderate impact.
- T36A (p.Thr36Ala), TOPMed rs1051372734, gnomAD rs1051372734, REVEL 0.22, CADD 21.60
- G37D (p.Gly37Asp), Ensembl rs2106015472
- D40A (p.Asp40Ala), Ensembl rs11689062
- E42Q (p.Glu42Gln), Ensembl rs2106015466
- G45A (p.Gly45Ala), Ensembl rs2106015447
- G45S (p.Gly45Ser), Ensembl rs2106015453
- G46E (p.Gly46Glu), Ensembl rs2106015442
- S47G (p.Ser47Gly), Ensembl rs2085287940
- S49I (p.Ser49Ile), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, Variant assessed as somatic; moderate impact.
- S49N (p.Ser49Asn), Ensembl rs2106015430
- R50K (p.Arg50Lys), Ensembl rs2106015416
- A52V (p.Ala52Val), cosmic curated COSV10590, Ensembl rs2106015407
- G53A (p.Gly53Ala), Ensembl rs2106015400
- V55M (p.Val55Met), rs774397512, ClinGen CA2043019, cosmic curated COSV59211, ClinVar RCV004341053, REVEL 0.19, CADD 22.00, Uncertain significance, not specified
- I58L (p.Ile58Leu), ExAC rs768672179, TOPMed rs768672179, gnomAD rs768672179
- I58V (p.Ile58Val), ExAC rs768672179, TOPMed rs768672179, gnomAD rs768672179, REVEL 0.16, CADD 23.30
- A59G (p.Ala59Gly), Ensembl rs2106015369
- A59T (p.Ala59Thr), cosmic curated COSV10942, Ensembl rs2085287542, REVEL 0.25, CADD 22.40
- A60V (p.Ala60Val), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, Ensembl rs2106015365, Variant assessed as somatic; moderate impact.
- E62K (p.Glu62Lys), Ensembl rs2106015357
- D67E (p.Asp67Glu), ESP rs148227154, ExAC rs148227154, TOPMed rs148227154, gnomAD rs148227154, REVEL 0.14, CADD 18.40
- D68E (p.Asp68Glu), Ensembl rs2085234481
- D68N (p.Asp68Asn), cosmic curated COSV59219, TOPMed rs1360783408, gnomAD rs1360783408, REVEL 0.17, CADD 23.20
- D69E (p.Asp69Glu), rs2085234371, ClinGen CA350206480, ClinVar RCV002287273, Ensembl rs2085234371, REVEL 0.07, CADD 19.30, Uncertain significance, Myelodysplastic syndrome
- D69G (p.Asp69Gly), TOPMed rs2085234427
- Y70* (p.Tyr70Ter), Ensembl rs2085234275, CADD 35.00
- Y70C (p.Tyr70Cys), ESP rs368842371, ExAC rs368842371, TOPMed rs368842371, gnomAD rs368842371, REVEL 0.15, CADD 23.40
- S71L (p.Ser71Leu), rs1261996759, NCI-TCGA Cosmic COSV5921, cosmic curated COSV59211, gnomAD rs1261996759, REVEL 0.25, CADD 23.60, Variant assessed as somatic; moderate impact.
- S72L (p.Ser72Leu), ExAC rs768864284, gnomAD rs768864284, REVEL 0.12, CADD 23.90
- S72P (p.Ser72Pro), TOPMed rs1300781021
- S73F (p.Ser73Phe), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, REVEL 0.11, CADD 23.30, Variant assessed as somatic; moderate impact.
- T74A (p.Thr74Ala), TOPMed rs1369580017
- T74M (p.Thr74Met), cosmic curated COSV10965, ExAC rs775351918, TOPMed rs775351918, gnomAD rs775351918, REVEL 0.22, CADD 23.20
- T74S (p.Thr74Ser), TOPMed rs1369580017
- S75N (p.Ser75Asn), cosmic curated COSV10590, ExAC rs745690210, gnomAD rs745690210, REVEL 0.06, CADD 19.60
- L77F (p.Leu77Phe), Ensembl rs2106011415
- K80N (p.Lys80Asn), Ensembl rs2106011405
- P82L (p.Pro82Leu), TOPMed rs1380493824, gnomAD rs1380493824, REVEL 0.15, CADD 23.40
- P82R (p.Pro82Arg), TOPMed rs1380493824, gnomAD rs1380493824
- G83E (p.Gly83Glu), Ensembl rs2106011390
- Y84C (p.Tyr84Cys), Ensembl rs2106011381, REVEL 0.74, CADD 29.00
- H85D (p.His85Asp), TOPMed rs1183412030, gnomAD rs1183412030, REVEL 0.15, CADD 22.50
- H85L (p.His85Leu), TOPMed rs1472004245, gnomAD rs1472004245, REVEL 0.25, CADD 24.00
- H85R (p.His85Arg), TOPMed rs1472004245, gnomAD rs1472004245, REVEL 0.15, CADD 22.50
- A86D (p.Ala86Asp), ExAC rs770523362, gnomAD rs770523362
- A86G (p.Ala86Gly), ExAC rs770523362, gnomAD rs770523362, REVEL 0.13, CADD 23.10
- A86T (p.Ala86Thr), NCI-TCGA Cosmic COSV5921, cosmic curated COSV59210, REVEL 0.67, CADD 25.90, Variant assessed as somatic; moderate impact.
- A86V (p.Ala86Val), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, ExAC rs770523362, gnomAD rs770523362, Variant assessed as somatic; moderate impact.
- P87L (p.Pro87Leu), gnomAD rs1024741639, REVEL 0.36, CADD 24.50
- P87S (p.Pro87Ser), cosmic curated COSV59230, 1000Genomes rs537380381, ExAC rs537380381, TOPMed rs537380381, REVEL 0.19, CADD 22.60
- V88M (p.Val88Met), ExAC rs777196787, TOPMed rs777196787, gnomAD rs777196787, REVEL 0.18, CADD 23.70
- D93G (p.Asp93Gly), gnomAD rs1372899073, REVEL 0.11, CADD 24.40
- D93N (p.Asp93Asn), Ensembl rs2085232970
- I94V (p.Ile94Val), ExAC rs757970228, gnomAD rs757970228, REVEL 0.21, CADD 20.20
- P95S (p.Pro95Ser), gnomAD rs1430821462
- T98A (p.Thr98Ala), TOPMed rs1221785624, REVEL 0.09, CADD 20.90
- E99G (p.Glu99Gly), NCI-TCGA Cosmic COSV5920, cosmic curated COSV59206, Variant assessed as somatic; moderate impact.
- Y101C (p.Tyr101Cys), rs1234164862, NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, TOPMed rs1234164862, REVEL 0.13, CADD 25.00, Variant assessed as somatic; moderate impact.
- Y101F (p.Tyr101Phe), TOPMed rs1234164862, gnomAD rs1234164862, REVEL 0.12, CADD 22.90
- D102A (p.Asp102Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P103L (p.Pro103Leu), Ensembl rs1574548280, REVEL 0.39, CADD 26.00
- F104L (p.Phe104Leu), gnomAD rs1299660208, REVEL 0.37, CADD 22.50
- A105V (p.Ala105Val), Ensembl rs2106010613
- P109L (p.Pro109Leu), ESP rs142315543, ExAC rs142315543, TOPMed rs142315543, gnomAD rs142315543, REVEL 0.21, CADD 23.00
- P109T (p.Pro109Thr), gnomAD rs1393540919, REVEL 0.19, CADD 19.60
- P110A (p.Pro110Ala), gnomAD rs1401630281, REVEL 0.11, CADD 19.20
- P110S (p.Pro110Ser), NCI-TCGA Cosmic COSV5920, cosmic curated COSV59209, Variant assessed as somatic; moderate impact.
- K111N (p.Lys111Asn), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, Variant assessed as somatic; moderate impact.
- I112T (p.Ile112Thr), Ensembl rs2085222729, REVEL 0.72, CADD 23.90
- I112V (p.Ile112Val), ExAC rs746393674, gnomAD rs746393674, REVEL 0.28, CADD 22.30
- A113S (p.Ala113Ser), ESP rs369364118, ExAC rs369364118, TOPMed rs369364118, gnomAD rs369364118, REVEL 0.13, CADD 21.80
- A113T (p.Ala113Thr), ESP rs369364118, ExAC rs369364118, TOPMed rs369364118, gnomAD rs369364118
- A113V (p.Ala113Val), Ensembl rs2106010567, REVEL 0.30, CADD 23.30
- R115Q (p.Arg115Gln), Ensembl rs2085222549, REVEL 0.48, CADD 26.70
- R115W (p.Arg115Trp), cosmic curated COSV10965, ExAC rs757758244, gnomAD rs757758244, REVEL 0.57, CADD 31.00
- E118K (p.Glu118Lys), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, Variant assessed as somatic; moderate impact.
- K120Q (p.Lys120Gln), NCI-TCGA Cosmic COSV5921, cosmic curated COSV59214, Variant assessed as somatic; moderate impact.
- H122R (p.His122Arg), ExAC rs758679975, gnomAD rs758679975, REVEL 0.09, CADD 16.50
- H122Y (p.His122Tyr), Ensembl rs2106010535
- R123G (p.Arg123Gly), gnomAD rs1179373486, REVEL 0.42, CADD 26.00
- R123M (p.Arg123Met), Ensembl rs2106010526
- R123T (p.Arg123Thr), Ensembl rs2106010526
- R124L (p.Arg124Leu), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10013, NCI-TCGA Cosmic COSV5921, Variant assessed as somatic; moderate impact.
- R124Q (p.Arg124Gln), NCI-TCGA Cosmic COSV1001, NCI-TCGA Cosmic COSV5921, cosmic curated COSV59215, Ensembl rs2106010524, REVEL 0.12, CADD 22.50, Variant assessed as somatic; moderate impact.
- R124W (p.Arg124Trp), cosmic curated COSV10812, NCI-TCGA TCGA novel, Ensembl rs2085222183, REVEL 0.23, CADD 23.70, Variant assessed as somatic; moderate impact.
- M126V (p.Met126Val), Ensembl rs1176548611, REVEL 0.32, CADD 21.20
- I127L (p.Ile127Leu), ExAC rs765373981, gnomAD rs765373981, REVEL 0.29, CADD 22.50
- I127V (p.Ile127Val), ExAC rs765373981, gnomAD rs765373981
- E131D (p.Glu131Asp), TOPMed rs2085221914
- R132C (p.Arg132Cys), cosmic curated COSV59209, Ensembl rs2106010499, REVEL 0.61, CADD 32.00
- R132H (p.Arg132His), cosmic curated COSV99065, Ensembl rs2106010494, REVEL 0.62, CADD 26.40, Uncertain significance, SF3B1-related disorder
- L133I (p.Leu133Ile), Ensembl rs2106010488
- L133V (p.Leu133Val), Ensembl rs2106010488
- D138N (p.Asp138Asn), Ensembl rs2106010474
- G139E (p.Gly139Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K141N (p.Lys141Asn), 1000Genomes rs788023, ESP rs788023, ExAC rs788023, TOPMed rs788023, REVEL 0.14, CADD 22.50, Benign
- K141K (p.Lys141Lys), rs788023, []
- T142A (p.Thr142Ala), gnomAD rs1196005307
- T142P (p.Thr142Pro), gnomAD rs1196005307
- P145H (p.Pro145His), Ensembl rs2085191509
- M147I (p.Met147Ile), ExAC rs768032201, gnomAD rs768032201, REVEL 0.15, CADD 21.50
- M147T (p.Met147Thr), gnomAD rs1426378138, REVEL 0.22, CADD 19.20
- M147V (p.Met147Val), NCI-TCGA Cosmic COSV1001, Ensembl rs2085191437, REVEL 0.08, CADD 17.40, Variant assessed as somatic; moderate impact.
- Y152F (p.Tyr152Phe), Ensembl rs1559274216, REVEL 0.12, CADD 22.30
- M153R (p.Met153Arg), gnomAD rs1214437688, REVEL 0.30, CADD 22.10
- M153V (p.Met153Val), TOPMed rs1271844302, gnomAD rs1271844302, REVEL 0.06, CADD 20.10
- V155A (p.Val155Ala), NCI-TCGA Cosmic COSV1001, Variant assessed as somatic; moderate impact.
- V155I (p.Val155Ile), Ensembl rs2085191095
- V155L (p.Val155Leu), Ensembl rs2085191095
- R157* (p.Arg157Ter), Ensembl rs868198796
- E158K (p.Glu158Lys), Ensembl rs2106007866
- H160N (p.His160Asn), ExAC rs747533615, gnomAD rs747533615, REVEL 0.05, CADD 22.50
- H160R (p.His160Arg), gnomAD rs1401350614, REVEL 0.13, CADD 22.20
- H160Y (p.His160Tyr), ExAC rs747533615, gnomAD rs747533615
- L161M (p.Leu161Met), NCI-TCGA Cosmic COSV1001, Variant assessed as somatic; moderate impact.
- T162S (p.Thr162Ser), gnomAD rs1340721089, REVEL 0.08, CADD 22.10
- E164K (p.Glu164Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E165D (p.Glu165Asp), ExAC rs772553108, TOPMed rs772553108, gnomAD rs772553108
- R166* (p.Arg166Ter), Ensembl rs2106005199
- R166L (p.Arg166Leu), gnomAD rs542810619, REVEL 0.12, CADD 32.00
- R166Q (p.Arg166Gln), gnomAD rs542810619, REVEL 0.10, CADD 23.70
- I168M (p.Ile168Met), TOPMed rs761530701, gnomAD rs761530701, REVEL 0.11, CADD 22.50
- I168N (p.Ile168Asn), Ensembl rs2106005191
- R169K (p.Arg169Lys), gnomAD rs2085155669, REVEL 0.18, CADD 22.20
- R169M (p.Arg169Met), gnomAD rs2085155669
Public SF3B1 analysis runs
- SF3B1 analysis run — SF3B1 (2,363 variants) — completed 2026-08-18