ABL1 (Tyrosine-protein kinase ABL1) variants and mutations
ABL1 (also known as Tyrosine-protein kinase ABL1) is a human protein-coding gene encoding a tyrosine-protein kinase protein. It coordinates cytoskeletal remodeling, adhesion, DNA-damage responses, and growth signaling through tightly regulated tyrosine phosphorylation. Fusion with BCR removes normal control and creates the constitutively active kinase that drives chronic myeloid leukemia and subsets of acute lymphoblastic leukemia. This analysis covers 2,305 ABL1 variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes chronic myelogenous leukemia, BCR-ABL1 positive, congenital heart defects and skeletal malformations syndrome, and acute lymphoblastic leukemia. Example ABL1 variants include L2M, L2L, and L2V.
Variant analysis overview
- Gene: ABL1
- Protein: Tyrosine-protein kinase ABL1
- UniProt accession: P00519
- Organism: Homo sapiens
- Variants analyzed: 2305
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,118 unspecified-consequence records; 112 missense variants; 63 synonymous variants; 3 frameshift variants; 2 in-frame insertions; 2 splice-region variants; 4 stop-gained variants; 1 substitution
- Prediction scores: 1,826 variants have prediction scores (79% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: chronic myelogenous leukemia, BCR-ABL1 positive, congenital heart defects and skeletal malformations syndrome, acute lymphoblastic leukemia, neoplasm, blast phase chronic myelogenous leukemia, BCR-ABL1 positive, gastrointestinal stromal tumor, colorectal cancer, dermatofibrosarcoma protuberans, hypereosinophilic syndrome, myelodysplastic/myeloproliferative disease, follicular lymphoma, neurodegenerative disease.
Protein structure and variant hotspots
- Protein features: 3 domains; 3 binding sites; 34 post-translational modification sites.
- Structural context: 674 variants have structural context.
- PTM context: 66 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 ABL1 variants
Examples include L2M, L2L, L2V, L2W, L2F, E3*, E3A, E3D. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- L2M (p.Leu2Met), gnomAD rs1479537095, REVEL 0.38, MetaLR 0.25
- L2L (p.Leu2Leu), gnomAD 9-130835450-T-C, CADD 20.90
- L2V (p.Leu2Val), gnomAD 9-130835450-T-G, REVEL 0.28, MetaLR 0.20
- L2W (p.Leu2Trp), gnomAD 9-130835451-T-G, REVEL 0.33, MetaLR 0.21
- L2F (p.Leu2Phe), gnomAD 9-130835452-G-T, REVEL 0.35, MetaLR 0.24
- E3* (p.Glu3Ter), gnomAD rs1430184898, CADD 21.10
- E3A (p.Glu3Ala), ESP rs369076507, ExAC rs369076507, gnomAD rs369076507, REVEL 0.28, MetaLR 0.19
- E3D (p.Glu3Asp), ExAC rs750562445, TOPMed rs750562445, gnomAD rs750562445, cosmic curated COSV59344, REVEL 0.12, MetaLR 0.18
- E3K (p.Glu3Lys), gnomAD 9-130835453-G-A, REVEL 0.28, MetaLR 0.18
- E3G (p.Glu3Gly), gnomAD 9-130835454-A-G, REVEL 0.33, MetaLR 0.19
- E3V (p.Glu3Val), gnomAD 9-130835454-A-T, REVEL 0.39, MetaLR 0.20
- E3E (p.Glu3Glu), rs750562445, gnomAD 9-130835455-G-A, CADD 18.00
- I4M (p.Ile4Met), rs749258648, gnomAD 9-130714388-C-G, MetaLR 0.42, MetaSVM -0.33
- I4V (p.Ile4Val), gnomAD 9-130835456-A-G, REVEL 0.36, MetaLR 0.33
- I4N (p.Ile4Asn), gnomAD 9-130835457-T-A, REVEL 0.46, MetaLR 0.40
- I4I (p.Ile4Ile), gnomAD 9-130835458-C-A, CADD 15.90
- C5Y (p.Cys5Tyr), cosmic curated COSV59326, REVEL 0.38, MetaLR 0.19
- C5R (p.Cys5Arg), gnomAD 9-130835459-T-C, REVEL 0.46, MetaLR 0.20
- C5F (p.Cys5Phe), gnomAD 9-130835460-G-T, REVEL 0.35, MetaLR 0.18
- C5* (p.Cys5Ter), gnomAD 9-130835461-C-A, CADD 18.50
- C5C (p.Cys5Cys), rs1830557952, gnomAD 9-130835461-C-T, CADD 19.00
- L6V (p.Leu6Val), TOPMed rs1012244732, gnomAD rs1012244732, REVEL 0.31, MetaLR 0.38
- L6M (p.Leu6Met), gnomAD 9-130835462-C-A, REVEL 0.35, MetaLR 0.38
- L6Q (p.Leu6Gln), gnomAD 9-130835463-T-A, REVEL 0.52, MetaLR 0.41
- L6P (p.Leu6Pro), gnomAD 9-130835463-T-C, REVEL 0.54, MetaLR 0.41
- L6L (p.Leu6Leu), gnomAD 9-130835464-G-T, CADD 19.80
- K7E (p.Lys7Glu), rs1158910186, gnomAD 9-130714338-A-G, MetaLR 0.32, MetaSVM -0.33
- K7R (p.Lys7Arg), rs375730000, gnomAD 9-130714339-A-G, MetaLR 0.23, MetaSVM -0.75
- K7T (p.Lys7Thr), gnomAD 9-130835466-A-C, REVEL 0.56, MetaLR 0.34
- K7K (p.Lys7Lys), gnomAD 9-130835467-G-A, CADD 20.80
- K7N (p.Lys7Asn), gnomAD 9-130835467-G-C, REVEL 0.39, MetaLR 0.35
- L8F (p.Leu8Phe), gnomAD 9-130714344-C-T, MetaLR 0.25, MetaSVM -0.60
- L8P (p.Leu8Pro), rs772507277, gnomAD 9-130714345-T-C, MetaLR 0.24, MetaSVM -0.78
- L8L (p.Leu8Leu), rs1831408812, gnomAD 9-130714346-T-C, CADD 12.50
- L8M (p.Leu8Met), gnomAD 9-130835468-C-A, REVEL 0.39, MetaLR 0.37
- L8Q (p.Leu8Gln), gnomAD 9-130835469-T-A, REVEL 0.52, MetaLR 0.41
- V9M (p.Val9Met), TOPMed rs1351762246, gnomAD rs1351762246, REVEL 0.48, MetaLR 0.34
- V9Y (p.Val9Tyr), rs2132661610, gnomAD 9-130714336-GA-G, CADD 26.20
- V9E (p.Val9Glu), rs774359039, gnomAD 9-130714342-T-A, MetaLR 0.26, MetaSVM -0.60
- V9G (p.Val9Gly), rs774359039, gnomAD 9-130714342-T-G, MetaLR 0.25, MetaSVM -0.52
- V9A (p.Val9Ala), rs774359039, gnomAD 9-130714342-T-C, MetaLR 0.27, MetaSVM -0.62
- V9W (p.Val9Trp), gnomAD 9-130835469-TG-T, CADD 18.50
- V9V (p.Val9Val), gnomAD 9-130835473-G-T, CADD 20.00
- G10D (p.Gly10Asp), Ensembl rs867708178, REVEL 0.55, MetaLR 0.34
- G10S (p.Gly10Ser), cosmic curated COSV59326, REVEL 0.48, MetaLR 0.26
- G10R (p.Gly10Arg), rs779924943, gnomAD 9-130714335-G-A, MetaLR 0.49, MetaSVM 0.03
- G10V (p.Gly10Val), gnomAD 9-130714336-G-T, MetaLR 0.57, MetaSVM 0.22
- G10A (p.Gly10Ala), rs749529951, gnomAD 9-130714336-G-C, MetaLR 0.55, MetaSVM 0.16
- G10G (p.Gly10Gly), gnomAD 9-130714337-A-T, CADD 13.90
- G10C (p.Gly10Cys), gnomAD 9-130835474-G-T, REVEL 0.61, MetaLR 0.34
- C11Y (p.Cys11Tyr), gnomAD rs1402615247, REVEL 0.62, MetaLR 0.38
- C11R (p.Cys11Arg), gnomAD 9-130835477-T-C, REVEL 0.58, MetaLR 0.36
- C11G (p.Cys11Gly), gnomAD 9-130835477-T-G, REVEL 0.53, MetaLR 0.35
- C11S (p.Cys11Ser), gnomAD 9-130835477-T-A, REVEL 0.53, MetaLR 0.35
- C11F (p.Cys11Phe), gnomAD 9-130835478-G-T, REVEL 0.63, MetaLR 0.38
- C11* (p.Cys11Ter), gnomAD 9-130835479-C-A, CADD 19.60
- C11C (p.Cys11Cys), rs2132913377, gnomAD 9-130835479-C-T, CADD 20.10
- K12R (p.Lys12Arg), TOPMed rs1367430242, gnomAD rs1367430242, REVEL 0.34, MetaLR 0.29
- K12T (p.Lys12Thr), TOPMed rs1367430242, gnomAD rs1367430242, REVEL 0.45, MetaLR 0.32
- K12* (p.Lys12Ter), gnomAD 9-130835480-A-T, CADD 21.00
- K12I (p.Lys12Ile), gnomAD 9-130835481-A-T, REVEL 0.50, MetaLR 0.32
- K12K (p.Lys12Lys), rs1282120253, gnomAD 9-130835482-A-G, CADD 19.10
- S13P (p.Ser13Pro), TOPMed rs1228311670, gnomAD rs1228311670, REVEL 0.41, MetaLR 0.30
- S13Y (p.Ser13Tyr), gnomAD 9-130835484-C-A, REVEL 0.46, MetaLR 0.35
- S13F (p.Ser13Phe), gnomAD 9-130835484-C-T, REVEL 0.48, MetaLR 0.35
- S13S (p.Ser13Ser), gnomAD 9-130835485-C-G, CADD 16.10
- K14* (p.Lys14Ter), cosmic curated COSV59328
- K14E (p.Lys14Glu), gnomAD 9-130835486-A-G, REVEL 0.33, MetaLR 0.31
- K14M (p.Lys14Met), gnomAD 9-130835487-A-T, REVEL 0.38, MetaLR 0.33
- K14R (p.Lys14Arg), gnomAD 9-130835487-A-G, REVEL 0.29, MetaLR 0.29
- K14T (p.Lys14Thr), gnomAD 9-130835487-A-C, REVEL 0.34, MetaLR 0.31
- K14K (p.Lys14Lys), gnomAD 9-130835488-G-A, CADD 19.10
- K14N (p.Lys14Asn), gnomAD 9-130835488-G-T, REVEL 0.30, MetaLR 0.30
- K15M (p.Lys15Met), cosmic curated COSV59337, MetaLR 0.33, MetaSVM -0.33
- K15N (p.Lys15Asn), NCI-TCGA TCGA novel, REVEL 0.28, MetaLR 0.27, Variant assessed as somatic; moderate impact.
- K15Q (p.Lys15Gln), rs1831409314, gnomAD 9-130714404-A-C, MetaLR 0.23, MetaSVM -0.82
- K15K (p.Lys15Lys), rs888154781, gnomAD 9-130714406-G-A, CADD 11.40
- K15E (p.Lys15Glu), gnomAD 9-130835489-A-G, REVEL 0.34, MetaLR 0.28
- K15R (p.Lys15Arg), gnomAD 9-130835490-A-G, REVEL 0.30, MetaLR 0.30
- G16V (p.Gly16Val), cosmic curated COSV10519, REVEL 0.56, MetaLR 0.33
- G16A (p.Gly16Ala), rs766734270, gnomAD 9-130714399-G-C, MetaLR 0.53, MetaSVM -0.23
- G16E (p.Gly16Glu), rs766734270, gnomAD 9-130714399-G-A, MetaLR 0.56, MetaSVM 0.11
- G16G (p.Gly16Gly), gnomAD 9-130714400-G-A, CADD 12.60
- G16W (p.Gly16Trp), gnomAD 9-130835492-G-T, REVEL 0.61, MetaLR 0.34
- L17M (p.Leu17Met), Ensembl rs2132913402, REVEL 0.28, MetaLR 0.37
- L17Q (p.Leu17Gln), Ensembl rs2132913411
- L17V (p.Leu17Val), Ensembl rs2132913402, MetaLR 0.35, MetaSVM -0.44
- L17L (p.Leu17Leu), rs1368062708, gnomAD 9-130714368-T-C, CADD 11.00
- L17S (p.Leu17Ser), gnomAD 9-130714369-T-C, MetaLR 0.27, MetaSVM -0.65
- L17P (p.Leu17Pro), gnomAD 9-130835496-T-C, REVEL 0.37, MetaLR 0.35
- L17R (p.Leu17Arg), gnomAD 9-130835496-T-G, REVEL 0.40, MetaLR 0.33
- S18A (p.Ser18Ala), Ensembl rs2132913430, MetaLR 0.30, MetaSVM -0.70
- S18C (p.Ser18Cys), TOPMed rs1281390090, REVEL 0.40, MetaLR 0.35
- S18G (p.Ser18Gly), rs1406577029, gnomAD 9-130714365-A-G, MetaLR 0.30, MetaSVM -0.42
- S18T (p.Ser18Thr), rs1831408977, gnomAD 9-130714366-G-C, MetaLR 0.31, MetaSVM -0.57
- S18S (p.Ser18Ser), gnomAD 9-130714367-C-T, CADD 10.60
- S18P (p.Ser18Pro), gnomAD 9-130835498-T-C, REVEL 0.31, MetaLR 0.32
- S18Y (p.Ser18Tyr), gnomAD 9-130835499-C-A, REVEL 0.37, MetaLR 0.35
- S19* (p.Ser19Ter), gnomAD rs866428555, CADD 21.00
- S19L (p.Ser19Leu), gnomAD rs866428555, REVEL 0.37, MetaLR 0.37
- S19W (p.Ser19Trp), gnomAD 9-130835502-C-G, REVEL 0.51, MetaLR 0.38
- S19S (p.Ser19Ser), rs373323350, gnomAD 9-130835503-G-C, CADD 17.90
- S20F (p.Ser20Phe), gnomAD rs1306763809, REVEL 0.24, MetaLR 0.20
- S20T (p.Ser20Thr), gnomAD 9-130835504-T-A, REVEL 0.12, MetaLR 0.19
- S20P (p.Ser20Pro), gnomAD 9-130835504-T-C, REVEL 0.24, MetaLR 0.19
- S20Y (p.Ser20Tyr), gnomAD 9-130835505-C-A, REVEL 0.19, MetaLR 0.21
- S20S (p.Ser20Ser), rs1205782138, gnomAD 9-130835506-C-T, CADD 20.40
- S21P (p.Ser21Pro), gnomAD 9-130835507-T-C, REVEL 0.30, MetaLR 0.33
- S21T (p.Ser21Thr), gnomAD 9-130835507-T-A, REVEL 0.28, MetaLR 0.28
- S21Y (p.Ser21Tyr), gnomAD 9-130835508-C-A, REVEL 0.38, MetaLR 0.35
- S21F (p.Ser21Phe), gnomAD 9-130835508-C-T, REVEL 0.35, MetaLR 0.35
- S21S (p.Ser21Ser), gnomAD 9-130835509-C-A, CADD 19.50
- S22G (p.Ser22Gly), gnomAD 9-130835510-A-G, REVEL 0.24, MetaLR 0.18
- S22R (p.Ser22Arg), gnomAD 9-130835510-A-C, REVEL 0.39, MetaLR 0.18
- S22I (p.Ser22Ile), gnomAD 9-130835511-G-T, REVEL 0.35, MetaLR 0.24
- S22S (p.Ser22Ser), gnomAD 9-130835512-C-T, CADD 19.70
- C23R (p.Cys23Arg), rs756814023, gnomAD 9-130714434-T-C, MetaLR 0.46, MetaSVM -0.29
- C23Y (p.Cys23Tyr), rs2132661885, gnomAD 9-130714435-G-A, MetaLR 0.44, MetaSVM -0.47
- C23F (p.Cys23Phe), gnomAD 9-130835514-G-T, REVEL 0.41, MetaLR 0.16
- C23S (p.Cys23Ser), gnomAD 9-130835514-G-C, REVEL 0.28, MetaLR 0.15
- C23C (p.Cys23Cys), rs754309439, gnomAD 9-130835515-T-C, CADD 16.50
- Y24C (p.Tyr24Cys), gnomAD rs1489845439, REVEL 0.48, MetaLR 0.30
- Y24N (p.Tyr24Asn), gnomAD 9-130835516-T-A, REVEL 0.42, MetaLR 0.28
- Y24Y (p.Tyr24Tyr), rs1221789432, gnomAD 9-130835518-T-C, CADD 19.60
- Y24* (p.Tyr24Ter), gnomAD 9-130835518-T-A, CADD 19.20
- L25M (p.Leu25Met), gnomAD 9-130835519-C-A, REVEL 0.20, MetaLR 0.21
- L25P (p.Leu25Pro), gnomAD 9-130835520-T-C, REVEL 0.35, MetaLR 0.22
- L25Q (p.Leu25Gln), gnomAD 9-130835520-T-A, REVEL 0.42, MetaLR 0.24
- L25L (p.Leu25Leu), rs1830559562, gnomAD 9-130835521-G-A, CADD 20.60
- E26G (p.Glu26Gly), gnomAD 9-130835523-A-G, REVEL 0.27, MetaLR 0.18
- E26E (p.Glu26Glu), gnomAD 9-130835524-A-G, CADD 20.90
- E26D (p.Glu26Asp), gnomAD 9-130835524-A-C, REVEL 0.20, MetaLR 0.17
- E27D (p.Glu27Asp), cosmic curated COSV10964
- E27V (p.Glu27Val), NCI-TCGA Cosmic COSV5933, cosmic curated COSV59335, Variant assessed as somatic; moderate impact.
- A28D (p.Ala28Asp), TOPMed rs761750284, gnomAD rs761750284, REVEL 0.38, MetaLR 0.16
- A28T (p.Ala28Thr), TOPMed rs1412043510, gnomAD rs1412043510, MetaLR 0.13, MetaSVM -1.01
- A28V (p.Ala28Val), cosmic curated COSV59343, TOPMed rs761750284, gnomAD rs761750284, REVEL 0.31, MetaLR 0.10
- A28S (p.Ala28Ser), rs201019733, gnomAD 9-130714374-G-T, MetaLR 0.31, MetaSVM -0.54
- A28A (p.Ala28Ala), gnomAD 9-130714376-C-T, CADD 13.80
- A28G (p.Ala28Gly), gnomAD 9-130714396-C-G, MetaLR 0.30, MetaSVM -0.74
- L29F (p.Leu29Phe), Ensembl rs2132956050, REVEL 0.17, MetaLR 0.16
- L29L (p.Leu29Leu), rs1830933757, gnomAD 9-130854071-T-C, CADD 7.91
- Q30* (p.Gln30Ter), gnomAD rs1166841293, CADD 39.00
- Q30H (p.Gln30His), gnomAD rs1358531180, REVEL 0.08, MetaLR 0.05
- Q30K (p.Gln30Lys), gnomAD 9-130714326-C-A, MetaLR 0.35, MetaSVM -0.26
- Q30Q (p.Gln30Gln), rs2132661576, gnomAD 9-130714328-G-A, CADD 9.83
- R31Q (p.Arg31Gln), rs368476764, ClinGen CA5285160, cosmic curated COSV10810, ClinVar RCV002098639, REVEL 0.16, MetaLR 0.10, Likely benign, Congenital heart defects and skeletal malformations syndrome; Inborn genetic dis
- R31W (p.Arg31Trp), 1000Genomes rs202235231, ExAC rs202235231, TOPMed rs202235231, gnomAD rs202235231, REVEL 0.31, MetaLR 0.15, Uncertain significance, Inborn genetic diseases
- R31G (p.Arg31Gly), rs773795578, gnomAD 9-130714356-A-G, MetaLR 0.34, MetaSVM -0.64
- R31K (p.Arg31Lys), gnomAD 9-130714357-G-A, MetaLR 0.29, MetaSVM -0.58
- R31R (p.Arg31Arg), rs1831408899, gnomAD 9-130714361-G-A, CADD 13.50
- P32S (p.Pro32Ser), cosmic curated COSV59340, REVEL 0.41, MetaLR 0.17
- P32P (p.Pro32Pro), rs993694601, gnomAD 9-130714334-T-C, CADD 14.60
- P32L (p.Pro32Leu), gnomAD 9-130714363-C-T, MetaLR 0.39, MetaSVM -0.36
- P32R (p.Pro32Arg), gnomAD 9-130714363-C-G, MetaLR 0.38, MetaSVM -0.46
- V33I (p.Val33Ile), cosmic curated COSV59343, MetaLR 0.06, MetaSVM -0.98
- V33F (p.Val33Phe), rs750387075, gnomAD 9-130714440-G-T, MetaLR 0.35, MetaSVM -0.56
- V33V (p.Val33Val), gnomAD 9-130714442-T-G, CADD 1.34
- V33A (p.Val33Ala), rs368254620, gnomAD 9-130714447-T-C, MetaLR 0.18, MetaSVM -0.84
- p.Val33dup, gnomAD 9-130854079-C-CAG, CADD 21.20
- A34G (p.Ala34Gly), cosmic curated COSV59344
- A34P (p.Ala34Pro), cosmic curated COSV59330, REVEL 0.16, MetaLR 0.09
- A34V (p.Ala34Val), TOPMed rs1165776027, MetaLR 0.05, MetaSVM -1.07
- A34T (p.Ala34Thr), gnomAD 9-130854084-G-A, REVEL 0.05, MetaLR 0.06
- A34A (p.Ala34Ala), gnomAD 9-130854086-A-G, CADD 10.10
- S35C (p.Ser35Cys), Ensembl rs2132956133, REVEL 0.11, MetaLR 0.07
- S35L (p.Ser35Leu), gnomAD 9-130714411-C-T, MetaLR 0.29, MetaSVM -0.72
- S35S (p.Ser35Ser), rs754145313, gnomAD 9-130714412-A-G, CADD 9.22
- p.Ser32dup, gnomAD 9-130714412-A-ATC, CADD 15.20
- S35T (p.Ser35Thr), rs2132661825, gnomAD 9-130714413-T-A, MetaLR 0.25, MetaSVM -0.83
- S35A (p.Ser35Ala), gnomAD 9-130854087-T-G, REVEL 0.12, MetaLR 0.07
- D36N (p.Asp36Asn), rs1423422276, NCI-TCGA Cosmic COSV5933, cosmic curated COSV59338, TOPMed rs1423422276, REVEL 0.17, MetaLR 0.17, Variant assessed as somatic; moderate impact.
- D36D (p.Asp36Asp), rs2132661669, gnomAD 9-130714352-C-T, CADD 12.50
- F37L (p.Phe37Leu), TOPMed rs1830934296, gnomAD rs1830934296, REVEL 0.18, MetaLR 0.04, Uncertain significance, not provided
- F37V (p.Phe37Val), rs1830934244, ClinGen CA375256333, ClinVar RCV001961630, Ensembl rs1830934244, REVEL 0.21, MetaLR 0.05, Uncertain significance, not provided
- F37C (p.Phe37Cys), gnomAD 9-130714384-T-G, MetaLR 0.41, MetaSVM -0.30
- F37S (p.Phe37Ser), rs1831409984, gnomAD 9-130714444-T-C, MetaLR 0.36, MetaSVM -0.50
- E38D (p.Glu38Asp), cosmic curated COSV59343
- E38G (p.Glu38Gly), Ensembl rs2132956162
- E38V (p.Glu38Val), Ensembl rs2132956162, MetaLR 0.15, MetaSVM -0.89
Public ABL1 analysis runs
- ABL1 analysis run — ABL1 (2,305 variants) — completed 2026-08-18