TET2 (Methylcytosine dioxygenase TET2) variants and mutations
TET2 (also known as Methylcytosine dioxygenase TET2) is a human protein-coding gene encoding a methylcytosine dioxygenase protein. It oxidizes methylated cytosines and helps reshape DNA methylation during hematopoietic differentiation. Somatic loss-of-function variants are among the most common drivers of clonal hematopoiesis and occur frequently in myeloid malignancies. This analysis covers 5,473 TET2 variants and mutations. Of these, 53% have computational variant effect predictions. Disease context includes myelodysplastic syndrome, acute myeloid leukemia, and neoplasm. Example TET2 variants include E2D, E2E, and E2G.
Variant analysis overview
- Gene: TET2
- Protein: Methylcytosine dioxygenase TET2
- UniProt accession: Q6N021
- Organism: Homo sapiens
- Variants analyzed: 5473
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 5,063 unspecified-consequence records; 116 missense variants; 138 synonymous variants; 12 stop-gained variants; 1 splice-region variants; 135 frameshift variants; 7 in-frame deletions; 1 substitution
- Prediction scores: 2,907 variants have prediction scores (53% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: myelodysplastic syndrome, acute myeloid leukemia, neoplasm, immunodeficiency 75, chronic myelomonocytic leukemia, lymphoid neoplasm, myeloid neoplasm, ebv-positive nodal t- and nk-cell lymphoma, hematologic disorder, chronic myelogenous leukemia, BCR-ABL1 positive, prostate carcinoma, myeloproliferative disorder.
Protein structure and variant hotspots
- Protein features: 21 binding sites; 6 post-translational modification sites.
- PTM context: 20 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 TET2 variants
Examples include E2D, E2E, E2G, Q3H, Q3*, Q3R, Q3K, Q3P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2D (p.Glu2Asp), gnomAD 4-105190481-A-C, CADD 15.20, SIFT 0.25
- E2E (p.Glu2Glu), gnomAD 4-105190484-G-A, CADD 13.90
- E2G (p.Glu2Gly), gnomAD 4-105233947-A-G, REVEL 0.43, MetaLR 0.22
- Q3H (p.Gln3His), 1000Genomes rs183431550, ExAC rs183431550, TOPMed rs183431550, gnomAD rs183431550, REVEL 0.16, MetaLR 0.13, Likely benign
- Q3* (p.Gln3Ter), rs1725720500, gnomAD 4-105190476-C-T, CADD 19.30
- Q3R (p.Gln3Arg), gnomAD 4-105190477-A-G, CADD 16.60, SIFT 0.34
- Q3K (p.Gln3Lys), gnomAD 4-105190485-C-A, CADD 14.80, SIFT 0.59
- Q3P (p.Gln3Pro), rs142128221, gnomAD 4-105233902-A-C, CADD 16.90, SIFT 0.10
- Q3Q (p.Gln3Gln), rs901606519, gnomAD 4-105233903-A-G, CADD 9.36
- D4G (p.Asp4Gly), TOPMed rs1159766969
- D4H (p.Asp4His), gnomAD rs1465868048, REVEL 0.20, MetaLR 0.23, Uncertain significance
- D4Y (p.Asp4Tyr), gnomAD rs1465868048, REVEL 0.26, MetaLR 0.24, Uncertain significance, not specified
- D4N (p.Asp4Asn), gnomAD 4-105233922-G-A, CADD 19.00, SIFT 0.00
- D4V (p.Asp4Val), gnomAD 4-105233952-GA-G, CADD 27.00
- R5G (p.Arg5Gly), ExAC rs749172180, gnomAD rs749172180, REVEL 0.12, MetaLR 0.12
- R5T (p.Arg5Thr), 1000Genomes rs568091851, ExAC rs568091851, gnomAD rs568091851, REVEL 0.14, MetaLR 0.13, Uncertain significance, not provided
- R5R (p.Arg5Arg), rs200508474, gnomAD 4-105233957-A-G, CADD 10.30
- T6A (p.Thr6Ala), ExAC rs745910165, gnomAD rs745910165
- T6N (p.Thr6Asn), Ensembl rs1578668444
- N7S (p.Asn7Ser), TOPMed rs1050537380, gnomAD rs1050537380, REVEL 0.13, MetaLR 0.04
- N7N (p.Asn7Asn), rs1369646936, gnomAD 4-105233963-C-T, CADD 8.71
- H8D (p.His8Asp), rs147112198, ClinGen CA3031433, cosmic curated COSV10879, ClinVar RCV002938973, REVEL 0.26, MetaLR 0.26, Likely benign, not provided
- H8L (p.His8Leu), TOPMed rs1266451196
- H8N (p.His8Asn), ESP rs147112198, ExAC rs147112198, TOPMed rs147112198, gnomAD rs147112198, REVEL 0.15, MetaLR 0.23, Likely benign
- H8R (p.His8Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H8Y (p.His8Tyr), ESP rs147112198, ExAC rs147112198, TOPMed rs147112198, gnomAD rs147112198, REVEL 0.22, MetaLR 0.26, Likely benign
- H8P (p.His8Pro), gnomAD 4-105233965-A-C, REVEL 0.43, MetaLR 0.24
- H8H (p.His8His), rs1281520653, gnomAD 4-105233966-T-C, CADD 9.04
- V9I (p.Val9Ile), cosmic curated COSV54409, TOPMed rs1322914073, gnomAD rs1322914073, REVEL 0.13, MetaLR 0.08, Uncertain significance, not specified
- V9L (p.Val9Leu), gnomAD 4-105233919-G-C, CADD 17.40, SIFT 0.02
- V9M (p.Val9Met), rs1461050148, gnomAD 4-105233919-G-A, CADD 17.80, SIFT 0.05
- V9A (p.Val9Ala), rs1199497103, gnomAD 4-105233920-T-C, CADD 19.50, SIFT 0.00
- V9V (p.Val9Val), rs767237496, gnomAD 4-105233921-G-A, CADD 20.20
- E10K (p.Glu10Lys), Ensembl rs2110219303
- E10Q (p.Glu10Gln), NCI-TCGA Cosmic COSV5443, cosmic curated COSV54431, Variant assessed as somatic; moderate impact.
- E10V (p.Glu10Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E10E (p.Glu10Glu), rs762224280, gnomAD 4-105233909-G-A, CADD 18.00
- E10D (p.Glu10Asp), rs762224280, gnomAD 4-105233909-G-C, CADD 17.80, SIFT 0.05
- E10G (p.Glu10Gly), gnomAD 4-105233971-A-G, REVEL 0.11, MetaLR 0.10
- G11D (p.Gly11Asp), ExAC rs747188735, gnomAD rs747188735, CADD 18.20, SIFT 0.01
- G11R (p.Gly11Arg), ExAC rs775632921, gnomAD rs775632921, CADD 18.10, SIFT 0.01
- G11S (p.Gly11Ser), ExAC rs775632921, gnomAD rs775632921, REVEL 0.32, MetaLR 0.31
- G11V (p.Gly11Val), ExAC rs747188735, gnomAD rs747188735, CADD 17.80, SIFT 0.14
- G11G (p.Gly11Gly), gnomAD 4-105233912-C-A, CADD 17.50
- N12S (p.Asn12Ser), TOPMed rs1728668700, gnomAD rs1728668700, REVEL 0.12, MetaLR 0.05, Uncertain significance, not specified
- N12N (p.Asn12Asn), rs1578668513, gnomAD 4-105233978-C-T, CADD 8.53
- R13K (p.Arg13Lys), cosmic curated COSV10502, REVEL 0.10, MetaLR 0.10
- R13G (p.Arg13Gly), gnomAD 4-105233979-A-G, REVEL 0.15, MetaLR 0.08
- R13R (p.Arg13Arg), rs146373819, gnomAD 4-105233979-A-C, CADD 10.40
- L14P (p.Leu14Pro), NCI-TCGA Cosmic COSV9948, cosmic curated COSV99482, Uncertain significance, not specified
- L14I (p.Leu14Ile), gnomAD 4-105233904-C-A, CADD 10.80, SIFT 0.56
- L14L (p.Leu14Leu), rs1728662884, gnomAD 4-105233906-A-G, CADD 9.04
- L14V (p.Leu14Val), gnomAD 4-105233982-C-G, REVEL 0.15, MetaLR 0.15
- S15I (p.Ser15Ile), cosmic curated COSV54411, REVEL 0.36, MetaLR 0.21
- S15N (p.Ser15Asn), gnomAD rs1436240000, REVEL 0.19, MetaLR 0.21
- S15T (p.Ser15Thr), gnomAD 4-105233914-G-C, CADD 17.40, SIFT 0.01
- S15S (p.Ser15Ser), rs754555616, gnomAD 4-105233915-C-T, CADD 18.80
- S15R (p.Ser15Arg), gnomAD 4-105233915-C-A, CADD 18.10, SIFT 0.03
- P16A (p.Pro16Ala), Ensembl rs2110219369
- P16L (p.Pro16Leu), cosmic curated COSV99483
- P16S (p.Pro16Ser), cosmic curated COSV54431
- P16P (p.Pro16Pro), rs752297092, gnomAD 4-105233930-C-T, CADD 16.10
- F17F (p.Phe17Phe), rs1204300917, gnomAD 4-105233993-C-T, CADD 9.60
- L18L (p.Leu18Leu), rs1391966054, gnomAD 4-105233942-G-C, CADD 18.00
- I19K (p.Ile19Lys), gnomAD rs1247584944, REVEL 0.14, MetaLR 0.07
- I19L (p.Ile19Leu), TOPMed rs1286727147, gnomAD rs1286727147, REVEL 0.07, MetaLR 0.05, Uncertain significance, not specified
- I19T (p.Ile19Thr), gnomAD rs1247584944, REVEL 0.03, MetaLR 0.04
- I19F (p.Ile19Phe), gnomAD 4-105190473-A-T, CADD 17.90, SIFT 0.01
- I19I (p.Ile19Ile), rs1310102705, gnomAD 4-105190475-C-T, CADD 17.80
- I19S (p.Ile19Ser), gnomAD 4-105233899-T-G, CADD 17.10, SIFT 0.00
- P20Q (p.Pro20Gln), Ensembl rs2110219423
- P20S (p.Pro20Ser), Ensembl rs2110219414
- P20T (p.Pro20Thr), gnomAD 4-105233998-T-TA, CADD 23.60
- P20L (p.Pro20Leu), gnomAD 4-105234001-C-T, REVEL 0.07, MetaLR 0.07
- P20P (p.Pro20Pro), gnomAD 4-105234002-A-G, CADD 5.19
- S21* (p.Ser21Ter), Ensembl rs1728670301
- S21P (p.Ser21Pro), cosmic curated COSV54427, REVEL 0.03, MetaLR 0.05
- S21L (p.Ser21Leu), gnomAD 4-105234004-C-T, REVEL 0.10, MetaLR 0.07
- P22L (p.Pro22Leu), NCI-TCGA Cosmic COSV5442, cosmic curated COSV54427, Variant assessed as somatic; moderate impact.
- P22S (p.Pro22Ser), cosmic curated COSV10808, TOPMed rs1728670474, REVEL 0.03, MetaLR 0.04, Uncertain significance, not specified
- P22T (p.Pro22Thr), cosmic curated COSV10609, REVEL 0.02, MetaLR 0.06, Uncertain significance, not specified
- P23L (p.Pro23Leu), ExAC rs776833011, TOPMed rs776833011
- P23R (p.Pro23Arg), ExAC rs776833011, TOPMed rs776833011, REVEL 0.06, MetaLR 0.07, Uncertain significance, not specified
- P23S (p.Pro23Ser), NCI-TCGA Cosmic COSV5440, cosmic curated COSV54407, Ensembl rs2110219448, REVEL 0.04, MetaLR 0.05, Variant assessed as somatic; moderate impact.
- I24Q (p.Ile24Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- I24V (p.Ile24Val), TOPMed rs1728670928, Uncertain significance, not specified
- I24I (p.Ile24Ile), gnomAD 4-105234014-T-A, CADD 4.43
- C25F (p.Cys25Phe), rs762289112, ClinGen CA3031438, NCI-TCGA Cosmic COSV5443, cosmic curated COSV54438, REVEL 0.12, MetaLR 0.12, Uncertain significance, not provided; not specified
- C25R (p.Cys25Arg), cosmic curated COSV54396
- C25Y (p.Cys25Tyr), ExAC rs762289112, TOPMed rs762289112, gnomAD rs762289112, Uncertain significance
- Q26* (p.Gln26Ter), cosmic curated COSV54433
- Q26H (p.Gln26His), cosmic curated COSV54421, Ensembl rs1728671297, Uncertain significance, not specified
- Q26R (p.Gln26Arg), cosmic curated COSV10502, REVEL 0.11, MetaLR 0.14
- T27I (p.Thr27Ile), NCI-TCGA Cosmic COSV5442, cosmic curated COSV54424, Variant assessed as somatic; moderate impact.
- T27R (p.Thr27Arg), rs765788512, ClinGen CA3031439, ClinVar RCV002801603, ClinVar RCV005288817, REVEL 0.11, MetaLR 0.11, Uncertain significance, not provided; not specified
- T27T (p.Thr27Thr), gnomAD 4-105234023-A-G, CADD 7.84
- E28A (p.Glu28Ala), ExAC rs773884315, TOPMed rs773884315, gnomAD rs773884315, REVEL 0.08, MetaLR 0.10
- E28G (p.Glu28Gly), ExAC rs773884315, TOPMed rs773884315, gnomAD rs773884315
- E28Q (p.Glu28Gln), NCI-TCGA TCGA novel, REVEL 0.09, MetaLR 0.08, Variant assessed as somatic; moderate impact.
- P29H (p.Pro29His), 1000Genomes rs12498609, ESP rs12498609, ExAC rs12498609, TOPMed rs12498609, Benign
- P29L (p.Pro29Leu), 1000Genomes rs12498609, ESP rs12498609, ExAC rs12498609, TOPMed rs12498609, REVEL 0.08, MetaLR 0.11, Benign
- P29R (p.Pro29Arg), rs12498609, ClinGen CA162345, cosmic curated COSV54402, ClinVar RCV000122131, REVEL 0.08, MetaLR 0.00, Benign, not specified; not provided
- P29A (p.Pro29Ala), gnomAD 4-105234027-C-G, REVEL 0.04, MetaLR 0.06
- P29P (p.Pro29Pro), gnomAD 4-105234029-T-C, CADD 10.20
- L30P (p.Leu30Pro), ExAC rs767145286, TOPMed rs767145286, gnomAD rs767145286, REVEL 0.18, MetaLR 0.15, Uncertain significance, not specified; not provided
- A31D (p.Ala31Asp), Ensembl rs2110219556
- A31P (p.Ala31Pro), gnomAD rs1728672596
- A31T (p.Ala31Thr), gnomAD rs1728672596, REVEL 0.07, MetaLR 0.19
- A31G (p.Ala31Gly), gnomAD 4-105233935-C-G, CADD 16.00, SIFT 0.01
- T32I (p.Thr32Ile), rs150238743, ClinGen CA3031442, ClinVar RCV002274689, ESP rs150238743, REVEL 0.03, MetaLR 0.03, Uncertain significance, not provided
- T32P (p.Thr32Pro), Ensembl rs2110219561
- T32S (p.Thr32Ser), Ensembl rs2110219561, REVEL 0.13, MetaLR 0.03, Uncertain significance, not specified
- T32A (p.Thr32Ala), gnomAD 4-105234036-A-G, REVEL 0.06, MetaLR 0.03
- K33E (p.Lys33Glu), TOPMed rs1728672951, REVEL 0.15, MetaLR 0.14, Uncertain significance, not specified
- L34F (p.Leu34Phe), rs111948941, ClinGen CA162305, cosmic curated COSV54412, ClinVar RCV000122123, REVEL 0.04, MetaLR 0.07, Benign, not specified; not provided
- L34P (p.Leu34Pro), gnomAD 4-105234043-T-C, REVEL 0.32, MetaLR 0.24
- L34L (p.Leu34Leu), gnomAD 4-105234044-C-G, CADD 7.31
- Q35* (p.Gln35Ter), cosmic curated COSV54436, CADD 36.00
- Q35K (p.Gln35Lys), cosmic curated COSV99484
- Q35H (p.Gln35His), gnomAD 4-105234047-G-T, REVEL 0.11, MetaLR 0.17
- N36K (p.Asn36Lys), Ensembl rs2110219608
- G37R (p.Gly37Arg), Ensembl rs2110219615
- G37E (p.Gly37Glu), gnomAD 4-105234052-G-A, REVEL 0.55, MetaLR 0.31
- S38G (p.Ser38Gly), ExAC rs763846739, gnomAD rs763846739, REVEL 0.06, MetaLR 0.08
- S38I (p.Ser38Ile), rs2110219622, ClinGen CA357790450, ClinVar RCV002807122, AlphaMissense 0.14, MetaLR 0.09, Uncertain significance, not provided
- S38R (p.Ser38Arg), cosmic curated COSV10879, ExAC rs753552413, gnomAD rs753552413, REVEL 0.07, MetaLR 0.07
- S38T (p.Ser38Thr), Ensembl rs2110219622
- P39L (p.Pro39Leu), rs1439284477, ClinGen CA357790469, ClinVar RCV002824786, ClinVar RCV005281233, REVEL 0.21, MetaLR 0.17, Uncertain significance, not specified; not provided
- P39Q (p.Pro39Gln), cosmic curated COSV99484
- P39S (p.Pro39Ser), ExAC rs757077124, gnomAD rs757077124, REVEL 0.32, MetaLR 0.26
- P39T (p.Pro39Thr), cosmic curated COSV10960
- L40P (p.Leu40Pro), cosmic curated COSV54411
- L40N (p.Leu40Asn), rs1560540209, gnomAD 4-105234058-C-CAA, CADD 25.00
- L40M (p.Leu40Met), gnomAD 4-105234060-C-A, REVEL 0.19, MetaLR 0.12
- L40Q (p.Leu40Gln), gnomAD 4-105234061-T-A, REVEL 0.20, MetaLR 0.14
- P41L (p.Pro41Leu), cosmic curated COSV10609, ExAC rs778756841, gnomAD rs778756841
- P41T (p.Pro41Thr), Ensembl rs769976230
- P41R (p.Pro41Arg), gnomAD 4-105234064-C-G, REVEL 0.09, MetaLR 0.06
- E42D (p.Glu42Asp), ExAC rs745818592, gnomAD rs745818592, REVEL 0.06, MetaLR 0.08
- E42* (p.Glu42Ter), gnomAD 4-105234066-G-T, CADD 35.00
- R43G (p.Arg43Gly), ExAC rs758392177, gnomAD rs758392177, REVEL 0.12, MetaLR 0.07
- R43I (p.Arg43Ile), cosmic curated COSV54411, TOPMed rs1728675224
- R43K (p.Arg43Lys), cosmic curated COSV10583
- A44T (p.Ala44Thr), TOPMed rs1728675394
- A44V (p.Ala44Val), ExAC rs779997538, gnomAD rs779997538
- H45Q (p.His45Gln), Ensembl rs2110219716
- H45R (p.His45Arg), gnomAD rs1728675742, REVEL 0.06, MetaLR 0.04
- H45Y (p.His45Tyr), cosmic curated COSV54433, REVEL 0.04, MetaLR 0.04
- H45D (p.His45Asp), gnomAD 4-105234075-C-G, REVEL 0.06, MetaLR 0.04
- H45P (p.His45Pro), gnomAD 4-105234076-A-C, REVEL 0.06, MetaLR 0.04
- P46L (p.Pro46Leu), rs376009634, NCI-TCGA Cosmic COSV5440, cosmic curated COSV54407, ESP rs376009634, REVEL 0.02, MetaLR 0.04, Variant assessed as somatic; moderate impact.
- P46R (p.Pro46Arg), ESP rs376009634, ExAC rs376009634, TOPMed rs376009634, gnomAD rs376009634, REVEL 0.02, MetaLR 0.04, Uncertain significance, not provided
- P46T (p.Pro46Thr), Ensembl rs2110219721, REVEL 0.03, MetaLR 0.04
- P46S (p.Pro46Ser), gnomAD 4-105234078-C-T, REVEL 0.04, MetaLR 0.04
- P46P (p.Pro46Pro), gnomAD 4-105234080-A-G, CADD 4.69
- E47* (p.Glu47Ter), cosmic curated COSV54438
- E47K (p.Glu47Lys), gnomAD 4-105234081-G-A, REVEL 0.19, MetaLR 0.12
- E47E (p.Glu47Glu), gnomAD 4-105234083-A-G, CADD 7.22
- V48I (p.Val48Ile), cosmic curated COSV10960
- V48* (p.Val48Ter), gnomAD 4-105234081-GA-G, CADD 24.10
- D51E (p.Asp51Glu), ExAC rs768741227, TOPMed rs768741227, gnomAD rs768741227, REVEL 0.03, MetaLR 0.05
- D51H (p.Asp51His), Ensembl rs2110219737
- D51N (p.Asp51Asn), Ensembl rs2110219737
- D51D (p.Asp51Asp), gnomAD 4-105234095-C-T, CADD 2.69
- T52I (p.Thr52Ile), gnomAD 4-105234097-C-T, REVEL 0.04, MetaLR 0.04
- T52T (p.Thr52Thr), gnomAD 4-105234098-C-T, CADD 6.50
- K53R (p.Lys53Arg), Ensembl rs1560540250, Uncertain significance, not specified
- K53P (p.Lys53Pro), gnomAD 4-105234093-G-GAC, CADD 25.20
- K53K (p.Lys53Lys), rs1728676612, gnomAD 4-105234101-G-A, CADD 5.71
- W54* (p.Trp54Ter), cosmic curated COSV10583, TOPMed rs1728676794, gnomAD rs1728676794, CADD 35.00
- W54R (p.Trp54Arg), Ensembl rs2110219770
- W54V (p.Trp54Val), gnomAD 4-105234098-C-CA, CADD 24.50
- H55L (p.His55Leu), ExAC rs781497651, TOPMed rs781497651, gnomAD rs781497651, REVEL 0.03, MetaLR 0.03
- H55P (p.His55Pro), ExAC rs781497651, TOPMed rs781497651, gnomAD rs781497651, REVEL 0.02, MetaLR 0.03, Uncertain significance, not specified
- H55Q (p.His55Gln), ExAC rs748418305, gnomAD rs748418305, REVEL 0.03, MetaLR 0.02
- H55Y (p.His55Tyr), gnomAD rs1291107913, REVEL 0.06, MetaLR 0.04
- H55R (p.His55Arg), gnomAD 4-105234106-A-G, REVEL 0.02, MetaLR 0.03
- S56C (p.Ser56Cys), ExAC rs770283635, gnomAD rs770283635, REVEL 0.13, MetaLR 0.07, Uncertain significance, not specified
- S56P (p.Ser56Pro), TOPMed rs1299382281, Uncertain significance, not provided
- S56Y (p.Ser56Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
Public TET2 analysis runs
- TET2 analysis run — TET2 (5,473 variants) — completed 2026-08-18