U2AF1 (Q01081) variants and mutations
U2AF1 (also known as Q01081) is a human protein-coding gene encoding a splicing factor U2AF 35 kDa subunit protein. It recognizes the AG dinucleotide at 3-prime splice sites during early spliceosome assembly. Recurrent S34 and Q157 hotspot mutations alter splice-site selection and are important drivers of myelodysplastic syndromes, AML, and some solid tumors. This analysis covers 642 U2AF1 variants and mutations. Of these, 66% have computational variant effect predictions. Disease context includes acute myeloid leukemia, lung adenocarcinoma, and neurodegenerative disease. Example U2AF1 variants include A2G, A2V, and A2A.
Variant analysis overview
- Gene: U2AF1
- Protein: Q01081
- UniProt accession: Q01081
- Organism: Homo sapiens
- Variants analyzed: 642
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 427 unspecified-consequence records; 113 missense variants; 76 synonymous variants; 8 stop-gained variants; 3 splice-region variants; 8 frameshift variants; 1 in-frame deletions; 6 substitution
- Prediction scores: 423 variants have prediction scores (66% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: acute myeloid leukemia, lung adenocarcinoma, neurodegenerative disease, myelodysplastic syndrome, non-small cell lung carcinoma, chronic myelomonocytic leukemia, lung carcinoma, chronic myelogenous leukemia, BCR-ABL1 positive, myelofibrosis, chronic neutrophilic leukemia, therapy related acute myeloid leukemia and myelodysplastic syndrome, hemangioblastoma.
Protein structure and variant hotspots
- Protein features: 1 domains; 8 post-translational modification sites.
- Structural context: 260 variants have structural context.
- PTM context: 18 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 U2AF1 variants
Examples include A2G, A2V, A2A, A2E, A2S, A2T, E3G, E3D. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2G (p.Ala2Gly), Ensembl rs2146474158, MetaLR 0.35, MetaSVM -0.14
- A2V (p.Ala2Val), Ensembl rs2146474158, REVEL 0.31, MetaLR 0.35
- A2A (p.Ala2Ala), gnomAD 21-43107489-C-A, CADD 15.80
- A2E (p.Ala2Glu), gnomAD 21-43107490-G-T, REVEL 0.35, MetaLR 0.42
- A2S (p.Ala2Ser), gnomAD 21-43107491-C-A, REVEL 0.22, MetaLR 0.32
- A2T (p.Ala2Thr), gnomAD 21-43107491-C-T, REVEL 0.25, MetaLR 0.37
- E3G (p.Glu3Gly), Ensembl rs2146474146, REVEL 0.16, MetaLR 0.29
- E3D (p.Glu3Asp), gnomAD 21-43107486-C-A, REVEL 0.07, MetaLR 0.13
- E3E (p.Glu3Glu), gnomAD 21-43107486-C-T, CADD 14.20
- E3K (p.Glu3Lys), gnomAD 21-43107488-C-T, REVEL 0.20, MetaLR 0.35
- E3Q (p.Glu3Gln), gnomAD 21-43107488-C-G, REVEL 0.10, MetaLR 0.24
- E3* (p.Glu3Ter), gnomAD 21-43107488-C-A, CADD 35.00
- Y4D (p.Tyr4Asp), gnomAD rs1305769409
- Y4Y (p.Tyr4Tyr), gnomAD 21-43107483-A-G, CADD 10.40
- L5L (p.Leu5Leu), rs1202241587, gnomAD 21-43107480-C-G, CADD 14.10
- L5P (p.Leu5Pro), gnomAD 21-43107481-A-G, REVEL 0.74, MetaLR 0.30
- L5M (p.Leu5Met), gnomAD 21-43107482-G-T, REVEL 0.29, MetaLR 0.40
- A6T (p.Ala6Thr), Ensembl rs868676340, REVEL 0.55, MetaLR 0.33
- A6A (p.Ala6Ala), gnomAD 21-43107477-G-T, CADD 14.10
- A6V (p.Ala6Val), gnomAD 21-43107478-G-A, REVEL 0.41, MetaLR 0.27
- A6P (p.Ala6Pro), gnomAD 21-43107478-GC-G, CADD 26.10
- A6D (p.Ala6Asp), gnomAD 21-43107478-G-T, REVEL 0.41, MetaLR 0.39
- A6S (p.Ala6Ser), gnomAD 21-43107479-C-A, REVEL 0.36, MetaLR 0.22
- S7S (p.Ser7Ser), gnomAD 21-43107474-G-T, CADD 14.40
- S7F (p.Ser7Phe), gnomAD 21-43107475-G-A, REVEL 0.29, MetaLR 0.36
- S7Y (p.Ser7Tyr), gnomAD 21-43107475-G-T, REVEL 0.36, MetaLR 0.26
- S7P (p.Ser7Pro), gnomAD 21-43107476-A-G, REVEL 0.33, MetaLR 0.38
- S7A (p.Ser7Ala), gnomAD 21-43107476-A-C, REVEL 0.12, MetaLR 0.15
- S7T (p.Ser7Thr), gnomAD 21-43107476-A-T, REVEL 0.19, MetaLR 0.25
- I8I (p.Ile8Ile), gnomAD 21-43107471-G-T, CADD 13.80
- F9L (p.Phe9Leu), gnomAD 21-43107468-G-T, REVEL 0.52, MetaLR 0.32
- F9F (p.Phe9Phe), gnomAD 21-43107468-G-A, CADD 15.50
- F9V (p.Phe9Val), gnomAD 21-43107470-A-C, REVEL 0.31, MetaLR 0.28
- G10R (p.Gly10Arg), Ensembl rs2146474074
- G10G (p.Gly10Gly), rs1392997771, gnomAD 21-43107465-G-A, CADD 15.70
- G10D (p.Gly10Asp), gnomAD 21-43107466-C-T, REVEL 0.26, MetaLR 0.36
- G10S (p.Gly10Ser), gnomAD 21-43107467-C-T, REVEL 0.29, MetaLR 0.23
- T11T (p.Thr11Thr), gnomAD 21-43107462-G-T, CADD 14.30
- T11I (p.Thr11Ile), gnomAD 21-43107463-G-A, REVEL 0.35, MetaLR 0.40
- T11N (p.Thr11Asn), gnomAD 21-43107463-G-T, REVEL 0.33, MetaLR 0.39
- E12K (p.Glu12Lys), cosmic curated COSV10962, Ensembl rs2146474046, REVEL 0.20, MetaLR 0.15
- E12Q (p.Glu12Gln), Ensembl rs2146474046, MetaLR 0.21, MetaSVM -0.74
- E12E (p.Glu12Glu), rs777812309, gnomAD 21-43107459-C-T, CADD 13.60
- E12D (p.Glu12Asp), gnomAD 21-43107459-C-A, REVEL 0.15, MetaLR 0.21
- E12G (p.Glu12Gly), gnomAD 21-43107460-T-C, REVEL 0.17, MetaLR 0.22
- E12* (p.Glu12Ter), gnomAD 21-43107461-C-A, CADD 35.00
- K13E (p.Lys13Glu), Ensembl rs2146474027
- K13K (p.Lys13Lys), rs1466277945, gnomAD 21-43107456-T-C, CADD 15.00
- K13R (p.Lys13Arg), gnomAD 21-43107457-T-C, REVEL 0.18, MetaLR 0.37
- D14E (p.Asp14Glu), Ensembl rs2146474014, REVEL 0.17, MetaLR 0.39
- D14D (p.Asp14Asp), gnomAD 21-43107453-G-A, CADD 23.00
- D14G (p.Asp14Gly), gnomAD 21-43107454-T-C, REVEL 0.38, MetaLR 0.42
- D14Y (p.Asp14Tyr), gnomAD 21-43107455-C-A, REVEL 0.81, MetaLR 0.54
- K15N (p.Lys15Asn), Ensembl rs2146468159, MetaLR 0.23, MetaSVM -0.66
- K15T (p.Lys15Thr), gnomAD 21-43107451-T-G, REVEL 0.27, MetaLR 0.19
- K15Q (p.Lys15Gln), gnomAD 21-43107452-T-G, REVEL 0.17, MetaLR 0.23
- K15E (p.Lys15Glu), gnomAD 21-43107452-T-C, REVEL 0.33, MetaLR 0.29
- V16D (p.Val16Asp), Ensembl rs2146468139
- V16F (p.Val16Phe), Ensembl rs2146468146
- V16I (p.Val16Ile), Ensembl rs2146468146
- V16L (p.Val16Leu), Ensembl rs2146468146
- N17I (p.Asn17Ile), Ensembl rs2146468102
- N17K (p.Asn17Lys), Ensembl rs2146468096
- N17S (p.Asn17Ser), Ensembl rs2146468102
- N17Y (p.Asn17Tyr), Ensembl rs2146468117
- C18* (p.Cys18Ter), Ensembl rs2146468067
- C18R (p.Cys18Arg), Ensembl rs2146468088
- C18S (p.Cys18Ser), Ensembl rs2146468075
- C18W (p.Cys18Trp), Ensembl rs2146468067
- C18Y (p.Cys18Tyr), Ensembl rs2146468075, MetaLR 1.00, MetaSVM 0.92
- S19* (p.Ser19Ter), Ensembl rs2146468052
- S19L (p.Ser19Leu), Ensembl rs2146468052
- S19T (p.Ser19Thr), Ensembl rs2146468060
- F20I (p.Phe20Ile), Ensembl rs2146468034
- F20V (p.Phe20Val), Ensembl rs2146468034
- F20Y (p.Phe20Tyr), Ensembl rs2146468028, MetaLR 0.40, MetaSVM 0.10
- Y21* (p.Tyr21Ter), Ensembl rs2146468023
- F22L (p.Phe22Leu), Ensembl rs2146468003
- F22Y (p.Phe22Tyr), Ensembl rs2146468015, MetaLR 0.11, MetaSVM -1.02
- K23* (p.Lys23Ter), Ensembl rs2146467995
- K23I (p.Lys23Ile), Ensembl rs2146467987, MetaLR 0.44, MetaSVM 0.20
- I24F (p.Ile24Phe), Ensembl rs2146467971
- I24V (p.Ile24Val), cosmic curated COSV52342, Ensembl rs2146467971, MetaLR 0.22, MetaSVM -0.77
- G25* (p.Gly25Ter), Ensembl rs2146467952
- G25R (p.Gly25Arg), Ensembl rs2146467952
- A26G (p.Ala26Gly), Ensembl rs2146467934, MetaLR 0.38, MetaSVM -0.07
- C27* (p.Cys27Ter), Ensembl rs2146467890
- C27F (p.Cys27Phe), Ensembl rs2146467903
- C27S (p.Cys27Ser), Ensembl rs2146467903
- C27W (p.Cys27Trp), Ensembl rs2146467890
- C27Y (p.Cys27Tyr), Ensembl rs2146467903, MetaLR 1.00, MetaSVM 0.92
- R28C (p.Arg28Cys), Ensembl rs2146467879
- R28G (p.Arg28Gly), cosmic curated COSV52348, Ensembl rs2146467879
- R28H (p.Arg28His), cosmic curated COSV52347, Ensembl rs2146467868
- R28P (p.Arg28Pro), Ensembl rs2146467868, MetaLR 0.34, MetaSVM -0.12
- H29D (p.His29Asp), Ensembl rs2146467850
- H29Q (p.His29Gln), Ensembl rs2146467833
- H29Y (p.His29Tyr), Ensembl rs2146467850
- G30A (p.Gly30Ala), Ensembl rs2146467809
- G30E (p.Gly30Glu), cosmic curated COSV10510, Ensembl rs2146467809
- G30V (p.Gly30Val), Ensembl rs2146467809, MetaLR 0.85, MetaSVM 0.96
- D31E (p.Asp31Glu), Ensembl rs1272473773
- D31H (p.Asp31His), cosmic curated COSV99374, Ensembl rs2146467795
- D31N (p.Asp31Asn), Ensembl rs2146467795
- D31V (p.Asp31Val), Ensembl rs2146467789, MetaLR 0.33, MetaSVM -0.33
- D31D (p.Asp31Asp), rs1272473773, gnomAD 21-43104354-G-A, CADD 12.80
- R32G (p.Arg32Gly), Ensembl rs2146467768
- R32K (p.Arg32Lys), Ensembl rs2146467758
- R32S (p.Arg32Ser), Ensembl rs200281496
- R32W (p.Arg32Trp), cosmic curated COSV10439, Ensembl rs2146467768, MetaLR 0.36, MetaSVM -0.24
- R32R (p.Arg32Arg), rs200281496, gnomAD 21-43104351-C-T, CADD 12.10
- C33* (p.Cys33Ter), ESP rs139959814, ExAC rs139959814, gnomAD rs139959814, Benign
- C33G (p.Cys33Gly), Ensembl rs2146467745
- C33S (p.Cys33Ser), Ensembl rs2146467745
- C33W (p.Cys33Trp), ESP rs139959814, ExAC rs139959814, gnomAD rs139959814, Benign
- C33Y (p.Cys33Tyr), Ensembl rs2146467738, MetaLR 1.00, MetaSVM 0.92
- C33C (p.Cys33Cys), rs139959814, gnomAD 21-43104348-G-A, CADD 12.40
- C33F (p.Cys33Phe), gnomAD 21-43104349-C-A, REVEL 0.97, MetaLR 1.00
- S34C (p.Ser34Cys), ESP rs371769427, ExAC rs371769427, gnomAD rs371769427
- S34F (p.Ser34Phe), rs371769427, cosmic curated COSV52341, ClinVar RCV006273212, UniProt VAR 079637, REVEL 0.70, AlphaMissense 1.00, Oncogenic, Neoplasm
- S34P (p.Ser34Pro), Ensembl rs2146467719
- S34Y (p.Ser34Tyr), rs371769427, cosmic curated COSV52341, UniProt VAR 079638, ESP rs371769427, AlphaMissense 1.00, MetaLR 0.41, Pathogenic, in MDS
- R35G (p.Arg35Gly), cosmic curated COSV52344, Ensembl rs2146467687
- R35Q (p.Arg35Gln), cosmic curated COSV52343, gnomAD rs1354293371
- R35W (p.Arg35Trp), Ensembl rs2146467687, MetaLR 0.37, MetaSVM -0.08
- R35L (p.Arg35Leu), gnomAD 21-43104343-C-A, REVEL 0.53, MetaLR 0.37
- R35R (p.Arg35Arg), gnomAD 21-43104344-G-T, CADD 13.80
- L36* (p.Leu36Ter), Ensembl rs2146467655
- L36F (p.Leu36Phe), Ensembl rs2146467648
- L36M (p.Leu36Met), Ensembl rs2146467663
- L36V (p.Leu36Val), Ensembl rs2146467663
- H37D (p.His37Asp), Ensembl rs2146467638
- H37L (p.His37Leu), Ensembl rs2146467630, REVEL 0.96, MetaLR 1.00
- H37Q (p.His37Gln), Ensembl rs2146467619
- H37Y (p.His37Tyr), Ensembl rs2146467638
- N38K (p.Asn38Lys), Ensembl rs1984676656, MetaLR 0.28, MetaSVM -0.46
- K39N (p.Lys39Asn), Ensembl rs2146467600, MetaLR 0.55, MetaSVM 0.26
- P40A (p.Pro40Ala), Ensembl rs2146467592
- P40Q (p.Pro40Gln), Ensembl rs2146467580
- P40R (p.Pro40Arg), Ensembl rs2146467580
- P40S (p.Pro40Ser), Ensembl rs2146467592, MetaLR 0.63, MetaSVM 0.52
- P40P (p.Pro40Pro), rs892764248, gnomAD 21-43104327-C-T, CADD 11.10
- T41M (p.Thr41Met), Ensembl rs2146467546
- T41P (p.Thr41Pro), Ensembl rs2146467563
- T41R (p.Thr41Arg), Ensembl rs2146467546
- T41S (p.Thr41Ser), Ensembl rs2146467563, MetaLR 0.53, MetaSVM 0.21
- T41K (p.Thr41Lys), gnomAD 21-43104325-G-T, REVEL 0.60, MetaLR 0.50
- F42L (p.Phe42Leu), Ensembl rs2146467521, MetaLR 0.43, MetaSVM -0.18
- S43I (p.Ser43Ile), Ensembl rs2146467502
- S43N (p.Ser43Asn), Ensembl rs2146467502
- S43R (p.Ser43Arg), Ensembl rs2146467492
- S43T (p.Ser43Thr), Ensembl rs2146467502, MetaLR 0.61, MetaSVM 0.47
- Q44* (p.Gln44Ter), Ensembl rs2146467485
- Q44E (p.Gln44Glu), Ensembl rs2146467485
- Q44H (p.Gln44His), gnomAD 21-43104315-C-A, REVEL 0.41, MetaLR 0.55
- A47V (p.Ala47Val), Ensembl rs2146463821, MetaLR 0.08, MetaSVM -1.10
- N50S (p.Asn50Ser), ExAC rs745966904, gnomAD rs745966904, MetaLR 0.39, MetaSVM -0.21
- Y52S (p.Tyr52Ser), Ensembl rs2146463800, MetaLR 0.56, MetaSVM 0.37
- R53C (p.Arg53Cys), Ensembl rs2146463783
- R53H (p.Arg53His), Ensembl rs2146463775, MetaLR 0.12, MetaSVM -1.02
- P55L (p.Pro55Leu), Ensembl rs2146463761, MetaLR 0.56, MetaSVM 0.32
- A62T (p.Ala62Thr), Ensembl rs2146463745
- A62V (p.Ala62Val), Ensembl rs2146463735, MetaLR 0.26, MetaSVM -0.72
- G64C (p.Gly64Cys), ExAC rs781134798, gnomAD rs781134798
- G64S (p.Gly64Ser), ExAC rs781134798, gnomAD rs781134798
- R66C (p.Arg66Cys), Ensembl rs2146463713, REVEL 0.15, MetaLR 0.12
- R66H (p.Arg66His), Ensembl rs2146463703, MetaLR 0.08, MetaSVM -1.00
- R66P (p.Arg66Pro), rs754274409, []
- A68V (p.Ala68Val), Ensembl rs2146456712, MetaLR 0.21, MetaSVM -0.79
- A68A (p.Ala68Ala), rs556591560, gnomAD 21-43095739-G-A, CADD 5.89, SIFT 0.00
- A68S (p.Ala68Ser), gnomAD 21-43095741-C-A, REVEL 0.24, MetaLR 0.15
- V69M (p.Val69Met), Ensembl rs2146456698
- S70R (p.Ser70Arg), ExAC rs747009029, gnomAD rs747009029, REVEL 0.64, MetaLR 0.38
- S70S (p.Ser70Ser), rs747009029, gnomAD 21-43095733-G-A, CADD 11.90
- S70C (p.Ser70Cys), gnomAD 21-43095735-T-A, REVEL 0.85, MetaLR 0.44
- D71D (p.Asp71Asp), gnomAD 21-43095730-A-G, CADD 8.17
- V72G (p.Val72Gly), gnomAD 21-43095728-A-C, REVEL 0.29, MetaLR 0.18
- E73D (p.Glu73Asp), Ensembl rs2146456686, MetaLR 0.22, MetaSVM -0.81
- Q75* (p.Gln75Ter), Ensembl rs2146456682
- Q75R (p.Gln75Arg), NCI-TCGA Cosmic COSV5235, cosmic curated COSV52351, Variant assessed as somatic; moderate impact.
Public U2AF1 analysis runs
- U2AF1 analysis run — U2AF1 (642 variants) — completed 2026-08-18