ASXL1 (Polycomb group protein ASXL1) variants and mutations
ASXL1 (also known as Polycomb group protein ASXL1) is a human protein-coding gene encoding a polycomb group protein. It regulates developmental and hematopoietic transcription through interactions with Polycomb and other chromatin-modifying systems. Somatic truncating variants are common in clonal hematopoiesis and myeloid malignancies, while germline pathogenic variants cause Bohring-Opitz syndrome. This analysis covers 4,107 ASXL1 variants and mutations. Of these, 51% have computational variant effect predictions. Disease context includes Bohring-Opitz syndrome, myelodysplastic syndrome, and acute myeloid leukemia. Example ASXL1 variants include M1L, M1I, and K2*.
Variant analysis overview
- Gene: ASXL1
- Protein: Polycomb group protein ASXL1
- UniProt accession: Q8IXJ9
- Organism: Homo sapiens
- Variants analyzed: 4107
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 4,004 unspecified-consequence records; 59 missense variants; 24 synonymous variants; 1 in-frame insertions; 2 in-frame deletions; 4 stop-gained variants; 2 splice-region variants; 2 frameshift variants; 7 substitution
- Prediction scores: 2,103 variants have prediction scores (51% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Bohring-Opitz syndrome, myelodysplastic syndrome, acute myeloid leukemia, myeloid neoplasm, neoplasm, myeloid leukemia, hematopoietic and lymphoid system neoplasm, lymphoid neoplasm, hereditary disease, nicotine dependence, Common Hematopoietic Neoplasm, primary myelofibrosis.
Protein structure and variant hotspots
- Protein features: 2 domains; 2 post-translational modification sites.
- Structural context: 450 variants have structural context.
- PTM context: 9 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, ClinGen, MaveDB, LitVar.
Notable ASXL1 variants
Examples include M1L, M1I, K2*, K2M, K2R, K2Q, K2E, K2K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs2122754733, ClinGen CA408575118, ClinVar RCV001582990, MetaLR 0.04, MetaSVM -1.07, Uncertain significance, not provided
- M1I (p.Met1Ile), rs952135039, []
- K2* (p.Lys2Ter), Ensembl rs2122754773, CADD 37.00
- K2M (p.Lys2Met), TOPMed rs2048056155, gnomAD rs2048056155, REVEL 0.08, CADD 26.10, Uncertain significance
- K2R (p.Lys2Arg), TOPMed rs2048056155, gnomAD rs2048056155, REVEL 0.10, CADD 24.70, Uncertain significance, Inborn genetic diseases
- K2Q (p.Lys2Gln), gnomAD 20-32358779-A-C, REVEL 0.10, CADD 26.00
- K2E (p.Lys2Glu), gnomAD 20-32358779-A-G, REVEL 0.09, CADD 25.70
- K2K (p.Lys2Lys), rs1192589790, gnomAD 20-32358781-G-A, CADD 13.80
- K2N (p.Lys2Asn), gnomAD 20-32358781-G-T, REVEL 0.07, CADD 27.20
- D3N (p.Asp3Asn), gnomAD rs1362206875, REVEL 0.09, CADD 26.10, Uncertain significance, Inborn genetic diseases
- D3Y (p.Asp3Tyr), gnomAD rs1362206875, REVEL 0.15, CADD 27.30
- D3G (p.Asp3Gly), gnomAD 20-32358783-A-G, REVEL 0.09, CADD 27.40
- D3D (p.Asp3Asp), gnomAD 20-32358784-C-T, CADD 13.60
- D3E (p.Asp3Glu), gnomAD 20-32358784-C-A, REVEL 0.10, CADD 19.10
- D3V (p.Asp3Val), rs1174053423, gnomAD 20-32359784-A-T, MetaLR 0.03, MetaSVM -0.99
- K4Q (p.Lys4Gln), gnomAD 20-32358785-A-C, REVEL 0.09, CADD 24.60
- K4R (p.Lys4Arg), gnomAD 20-32358786-A-G, REVEL 0.10, CADD 21.90
- K4K (p.Lys4Lys), gnomAD 20-32358787-A-G, CADD 13.90
- Q5R (p.Gln5Arg), TOPMed rs1254502448, REVEL 0.08, CADD 24.60
- Q5* (p.Gln5Ter), gnomAD 20-32358788-C-T, CADD 35.00
- Q5Q (p.Gln5Gln), gnomAD 20-32358790-G-A, CADD 13.40
- Q5H (p.Gln5His), gnomAD 20-32358790-G-T, REVEL 0.05, CADD 26.20
- Q5P (p.Gln5Pro), rs1470448926, gnomAD 20-32359333-A-C, CADD 14.50, SIFT 0.33
- Q5K (p.Gln5Lys), gnomAD 20-32359789-C-A, MetaLR 0.01, MetaSVM -0.95
- Q5E (p.Gln5Glu), rs1361350029, gnomAD 20-32359789-C-G, MetaLR 0.02, MetaSVM -0.95
- Q5L (p.Gln5Leu), rs905152720, gnomAD 20-32359790-A-T, MetaLR 0.02, MetaSVM -0.98
- K6E (p.Lys6Glu), NCI-TCGA TCGA novel, REVEL 0.04, CADD 26.10, Variant assessed as somatic; high impact.
- K6R (p.Lys6Arg), gnomAD 20-32358792-A-G, REVEL 0.05, CADD 23.60
- K6M (p.Lys6Met), gnomAD 20-32358792-A-T, REVEL 0.11, CADD 26.30
- K6K (p.Lys6Lys), rs2048056489, gnomAD 20-32358793-G-A, CADD 14.30
- K7* (p.Lys7Ter), gnomAD 20-32358794-A-T, CADD 37.00
- K7E (p.Lys7Glu), gnomAD 20-32358794-A-G, REVEL 0.05, CADD 24.00
- K7R (p.Lys7Arg), gnomAD 20-32358795-A-G, REVEL 0.03, CADD 16.80
- K8E (p.Lys8Glu), Ensembl rs2122754888, SIFT 0.00
- p.Lys8 Lys9del, rs752094508, gnomAD 20-32358788-CAGAA, CADD 18.20
- K8R (p.Lys8Arg), gnomAD 20-32358798-A-G, REVEL 0.07, CADD 24.00
- K8N (p.Lys8Asn), gnomAD 20-32358799-G-C, REVEL 0.09, CADD 26.90
- K8K (p.Lys8Lys), rs1420153033, gnomAD 20-32358799-G-A, CADD 14.80
- K9R (p.Lys9Arg), TOPMed rs886129274, gnomAD rs886129274, REVEL 0.08, CADD 26.30, Uncertain significance, Inborn genetic diseases
- K9E (p.Lys9Glu), gnomAD rs1292736851, REVEL 0.12, CADD 23.80
- p.Lys9dup, rs752094508, gnomAD 20-32358788-C-CAG, CADD 18.40
- K9del (p.Lys9del), rs752094508, gnomAD 20-32358788-CAGA-, CADD 19.30
- K9T (p.Lys9Thr), gnomAD 20-32358801-A-C, REVEL 0.10, CADD 25.20
- K9M (p.Lys9Met), gnomAD 20-32358801-A-T, REVEL 0.14, CADD 25.70
- K9N (p.Lys9Asn), gnomAD 20-32358802-G-T, REVEL 0.09, CADD 26.40
- K9K (p.Lys9Lys), gnomAD 20-32358802-G-A, CADD 13.80
- E10G (p.Glu10Gly), rs2515137140, ClinGen CA408575340, ClinVar RCV002816981, REVEL 0.07, CADD 25.70, Uncertain significance, Inborn genetic diseases
- E10K (p.Glu10Lys), gnomAD 20-32358803-G-A, REVEL 0.04, CADD 26.40
- E10* (p.Glu10Ter), gnomAD 20-32358803-G-T, CADD 37.00
- E10E (p.Glu10Glu), gnomAD 20-32358805-G-A, CADD 12.30
- E10D (p.Glu10Asp), gnomAD 20-32358805-G-T, REVEL 0.03, CADD 24.10
- R11C (p.Arg11Cys), cosmic curated COSV60111, Ensembl rs2122754952, REVEL 0.19, CADD 27.40, Uncertain significance, Inborn genetic diseases
- R11S (p.Arg11Ser), gnomAD 20-32358806-C-A, REVEL 0.16, CADD 25.30
- R11L (p.Arg11Leu), gnomAD 20-32358807-G-T, REVEL 0.18, CADD 25.90
- R11H (p.Arg11His), gnomAD 20-32358807-G-A, REVEL 0.13, CADD 27.10
- R11R (p.Arg11Arg), gnomAD 20-32358808-C-A, CADD 14.20
- R11G (p.Arg11Gly), gnomAD 20-32359771-A-G, MetaLR 0.03, MetaSVM -0.99
- T12S (p.Thr12Ser), gnomAD 20-32358809-A-T, REVEL 0.10, CADD 24.40
- T12A (p.Thr12Ala), gnomAD 20-32358809-A-G, REVEL 0.09, CADD 24.90
- T12K (p.Thr12Lys), gnomAD 20-32358810-C-A, REVEL 0.15, CADD 24.90
- T12R (p.Thr12Arg), gnomAD 20-32358810-C-G, REVEL 0.15, CADD 29.60
- T12M (p.Thr12Met), gnomAD 20-32358810-C-T, REVEL 0.10, CADD 25.00
- T12T (p.Thr12Thr), gnomAD 20-32358811-G-A, CADD 13.90
- W13* (p.Trp13Ter), Ensembl rs2122754984, CADD 39.00
- W13G (p.Trp13Gly), Ensembl rs2122754965, REVEL 0.31, CADD 27.40
- W13R (p.Trp13Arg), Ensembl rs2122754965, SIFT 0.00
- W13L (p.Trp13Leu), gnomAD 20-32358813-G-T, REVEL 0.29, CADD 24.50
- W13C (p.Trp13Cys), gnomAD 20-32358814-G-T, REVEL 0.35, CADD 29.50
- A14V (p.Ala14Val), rs1365687375, ClinGen CA408575401, ClinVar RCV002303417, ClinVar RCV005724787, REVEL 0.17, CADD 27.00, Conflicting interpretations, not provided; Inborn genetic diseases
- A14T (p.Ala14Thr), gnomAD 20-32358815-G-A, REVEL 0.13, CADD 26.70
- A14S (p.Ala14Ser), gnomAD 20-32358815-G-T, REVEL 0.10, CADD 25.40
- A14D (p.Ala14Asp), gnomAD 20-32358816-C-A, REVEL 0.19, CADD 25.50
- A14A (p.Ala14Ala), gnomAD 20-32358817-C-A, CADD 14.40
- E15G (p.Glu15Gly), Ensembl rs2122755016, REVEL 0.18, CADD 27.90
- E15K (p.Glu15Lys), TOPMed rs1464069229, gnomAD rs1464069229, REVEL 0.12, CADD 27.10
- E15* (p.Glu15Ter), gnomAD 20-32358818-G-T, CADD 38.00
- E15Q (p.Glu15Gln), gnomAD 20-32358818-G-C, REVEL 0.08, CADD 25.50
- E15V (p.Glu15Val), gnomAD 20-32358819-A-T, REVEL 0.17, CADD 23.80
- E15E (p.Glu15Glu), rs1388766224, gnomAD 20-32358820-G-A, CADD 13.10
- E15D (p.Glu15Asp), gnomAD 20-32358820-G-T, REVEL 0.09, CADD 23.10
- A16T (p.Ala16Thr), gnomAD 20-32358821-G-A, REVEL 0.13, CADD 23.80
- A16S (p.Ala16Ser), gnomAD 20-32358821-G-T, REVEL 0.14, CADD 23.70
- A16V (p.Ala16Val), gnomAD 20-32358822-C-T, REVEL 0.17, CADD 23.60
- A16D (p.Ala16Asp), gnomAD 20-32358822-C-A, REVEL 0.23, CADD 25.20
- A16A (p.Ala16Ala), rs2122755039, gnomAD 20-32358823-C-A, CADD 14.10
- A17G (p.Ala17Gly), Ensembl rs2122755047, REVEL 0.14, CADD 24.70
- A17T (p.Ala17Thr), gnomAD 20-32358824-G-A, REVEL 0.15, CADD 24.80
- A17S (p.Ala17Ser), gnomAD 20-32358824-G-T, REVEL 0.12, CADD 23.20
- A17V (p.Ala17Val), gnomAD 20-32358825-C-T, REVEL 0.11, CADD 23.00
- A17E (p.Ala17Glu), gnomAD 20-32358825-C-A, REVEL 0.19, CADD 23.30
- A17A (p.Ala17Ala), gnomAD 20-32358826-G-T, CADD 11.30
- R18L (p.Arg18Leu), rs2122755072, ClinGen CA408575467, ClinVar RCV001787649, Ensembl rs2122755072, AlphaMissense 0.84, MetaLR 0.05, Uncertain significance, not provided
- R18S (p.Arg18Ser), gnomAD rs1302023145, REVEL 0.20, CADD 24.70
- R18C (p.Arg18Cys), gnomAD 20-32358827-C-T, REVEL 0.14, CADD 27.00
- R18H (p.Arg18His), gnomAD 20-32358828-G-A, REVEL 0.08, CADD 25.80
- R18R (p.Arg18Arg), gnomAD 20-32358829-C-A, CADD 13.90
- L19V (p.Leu19Val), gnomAD rs2048057022, REVEL 0.03, CADD 23.00
- L19L (p.Leu19Leu), gnomAD 20-32358830-C-T, CADD 19.20
- L19R (p.Leu19Arg), gnomAD 20-32358831-T-G, REVEL 0.19, CADD 22.30
- L19P (p.Leu19Pro), gnomAD 20-32358831-T-C, REVEL 0.16, CADD 25.50
- V20A (p.Val20Ala), Ensembl rs2122809810
- V20E (p.Val20Glu), Ensembl rs2122809810
- V20I (p.Val20Ile), Ensembl rs2122809752
- V20L (p.Val20Leu), Ensembl rs2122809752, MetaLR 0.14, MetaSVM -1.01
- V20F (p.Val20Phe), gnomAD 20-32359753-G-T, MetaLR 0.04, MetaSVM -0.99
- V20C (p.Val20Cys), rs756234325, gnomAD 20-32359760-A-AT, CADD 14.90
- V20V (p.Val20Val), rs2048204813, gnomAD 20-32366386-A-T, CADD 7.32
- L21F (p.Leu21Phe), Ensembl rs2122809909
- L21I (p.Leu21Ile), Ensembl rs2122809885, MetaLR 0.23, MetaSVM -0.72
- E22* (p.Glu22Ter), Ensembl rs2122809937
- E22G (p.Glu22Gly), ExAC rs775831641, gnomAD rs775831641, REVEL 0.53, MetaLR 0.27, Uncertain significance, not provided; Inborn genetic diseases
- E22Q (p.Glu22Gln), Ensembl rs2122809937, Uncertain significance, not provided
- E22V (p.Glu22Val), ExAC rs775831641, gnomAD rs775831641, MetaLR 0.33, MetaSVM -0.46
- N23D (p.Asn23Asp), Ensembl rs2122810052, Uncertain significance, Inborn genetic diseases
- N23H (p.Asn23His), Ensembl rs2122810052
- N23I (p.Asn23Ile), Ensembl rs2122810108
- N23K (p.Asn23Lys), Ensembl rs2048204984
- N23S (p.Asn23Ser), NCI-TCGA TCGA novel, MetaLR 0.08, MetaSVM -1.11, Variant assessed as somatic; moderate impact.
- N23Y (p.Asn23Tyr), Ensembl rs2122810052, REVEL 0.33, MetaLR 0.09
- N23N (p.Asn23Asn), gnomAD 20-32366395-C-T, CADD 13.30
- Y24* (p.Tyr24Ter), Ensembl rs2122810224
- Y24C (p.Tyr24Cys), rs2122810196, ClinGen CA408577570, ClinVar RCV003570102, AlphaMissense 0.32, MetaLR 0.09, Uncertain significance, not provided
- Y24F (p.Tyr24Phe), Ensembl rs2122810196, MetaLR 0.09, MetaSVM -0.92
- S25* (p.Ser25Ter), gnomAD rs1219695894
- S25L (p.Ser25Leu), cosmic curated COSV60107, gnomAD rs1219695894, REVEL 0.16, MetaLR 0.12, Uncertain significance, Inborn genetic diseases
- S25P (p.Ser25Pro), TOPMed rs2048205129
- S25T (p.Ser25Thr), TOPMed rs2048205129
- S25W (p.Ser25Trp), gnomAD rs1219695894
- S25A (p.Ser25Ala), gnomAD 20-32359312-TG-T, CADD 13.90
- S25R (p.Ser25Arg), rs555982581, gnomAD 20-32359314-A-C, CADD 14.10, SIFT 0.12
- S25I (p.Ser25Ile), gnomAD 20-32359315-G-T, CADD 13.60, SIFT 0.18
- S25S (p.Ser25Ser), rs1377853058, gnomAD 20-32359316-C-T, CADD 4.96
- D26E (p.Asp26Glu), Ensembl rs2122810436
- D26H (p.Asp26His), Ensembl rs2122810366
- D26N (p.Asp26Asn), Ensembl rs2122810366
- D26Y (p.Asp26Tyr), Ensembl rs2122810366, MetaLR 0.32, MetaSVM -0.56
- D26G (p.Asp26Gly), gnomAD 20-32366403-A-G, REVEL 0.29, MetaLR 0.11
- A27P (p.Ala27Pro), Ensembl rs2122810467
- A27T (p.Ala27Thr), Ensembl rs2122810467, MetaLR 0.21, MetaSVM -0.86
- P28A (p.Pro28Ala), Ensembl rs2122810543
- P28L (p.Pro28Leu), Ensembl rs2122810580
- P28Q (p.Pro28Gln), Ensembl rs2122810580
- P28S (p.Pro28Ser), Ensembl rs2122810543
- P28T (p.Pro28Thr), Ensembl rs2122810543, MetaLR 0.36, MetaSVM -0.42
- P28H (p.Pro28His), gnomAD 20-32359321-C-A, CADD 8.61, SIFT 0.30
- P28P (p.Pro28Pro), rs1025634265, gnomAD 20-32359322-C-T, CADD 8.43
- M29I (p.Met29Ile), Ensembl rs2122810689
- M29L (p.Met29Leu), ExAC rs769223128, gnomAD rs769223128, Uncertain significance
- M29T (p.Met29Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M29V (p.Met29Val), rs769223128, ClinGen CA408577684, ClinVar RCV003670358, ExAC rs769223128, AlphaMissense 0.70, MetaLR 0.33, Uncertain significance, not provided
- T30A (p.Thr30Ala), TOPMed rs1378562189
- T30R (p.Thr30Arg), Ensembl rs2122810765
- T30S (p.Thr30Ser), TOPMed rs1378562189, MetaLR 0.13, MetaSVM -0.96
- P31A (p.Pro31Ala), gnomAD rs1178102908
- P31S (p.Pro31Ser), rs1178102908, gnomAD rs1178102908, REVEL 0.18, MetaLR 0.31, Variant assessed as somatic; moderate impact.
- P31T (p.Pro31Thr), gnomAD rs1178102908, MetaLR 0.31, MetaSVM -0.56
- K32* (p.Lys32Ter), Ensembl rs2122810944
- K32N (p.Lys32Asn), Ensembl rs2122810983, MetaLR 0.25, MetaSVM -0.70
- K32K (p.Lys32Lys), gnomAD 20-32366422-A-G, CADD 12.80
- Q33E (p.Gln33Glu), cosmic curated COSV60103, TOPMed rs1192808397
- Q33H (p.Gln33His), Ensembl rs2122811096
- Q33L (p.Gln33Leu), Ensembl rs2122811057
- Q33R (p.Gln33Arg), Ensembl rs2122811057, MetaLR 0.10, MetaSVM -1.06, Uncertain significance, Inborn genetic diseases
- I34N (p.Ile34Asn), Ensembl rs2122811137, MetaLR 0.20, MetaSVM -0.70
- L35M (p.Leu35Met), NCI-TCGA Cosmic COSV6010, cosmic curated COSV60107, Variant assessed as somatic; moderate impact.
- L35Q (p.Leu35Gln), Ensembl rs2122811214
- L35V (p.Leu35Val), Ensembl rs2122811194, MetaLR 0.34, MetaSVM -0.46
- Q36* (p.Gln36Ter), Ensembl rs2122811284
- Q36E (p.Gln36Glu), cosmic curated COSV60115, Ensembl rs2122811284
- Q36H (p.Gln36His), Ensembl rs2122811348
- Q36K (p.Gln36Lys), Ensembl rs2122811284
- Q36L (p.Gln36Leu), Ensembl rs2122811319, MetaLR 0.08, MetaSVM -1.12
- Q36R (p.Gln36Arg), Ensembl rs2122811319, REVEL 0.13, MetaLR 0.06
- Q36Q (p.Gln36Gln), rs2122811348, gnomAD 20-32366434-G-A, CADD 10.70
- V37A (p.Val37Ala), Ensembl rs2122811410
- V37D (p.Val37Asp), Ensembl rs2122811410
- V37G (p.Val37Gly), NCI-TCGA TCGA novel, Ensembl rs2122811410, Variant assessed as somatic; high impact.
- V37I (p.Val37Ile), gnomAD rs1378944067, REVEL 0.15, MetaLR 0.13
- V37L (p.Val37Leu), gnomAD rs1378944067, MetaLR 0.17, MetaSVM -0.83
- V37V (p.Val37Val), rs2048205685, gnomAD 20-32366437-C-T, CADD 11.10
Public ASXL1 analysis runs
- ASXL1 analysis run — ASXL1 (4,107 variants) — completed 2026-08-18