BCL2L1 (Bcl-2-like protein 1) variants and mutations
BCL2L1 (also known as Bcl-2-like protein 1) is a human protein-coding gene encoding a bcl-2-like protein 1 protein. Its major anti-apoptotic isoform, BCL-XL, restrains mitochondrial cell death by binding and neutralizing pro-apoptotic BCL-2-family proteins. Many cancers exploit elevated BCL-XL activity to survive cellular stress and therapy. This analysis covers 675 BCL2L1 variants and mutations. Of these, 60% have computational variant effect predictions. Disease context includes neurodegenerative disease, severe acute respiratory syndrome, and neoplasm. Example BCL2L1 variants include S2A, S2C, and S2F.
Variant analysis overview
- Gene: BCL2L1
- Protein: Bcl-2-like protein 1
- UniProt accession: Q07817
- Organism: Homo sapiens
- Variants analyzed: 675
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 432 unspecified-consequence records; 109 synonymous variants; 117 missense variants; 1 in-frame insertions; 5 frameshift variants; 8 stop-gained variants; 1 in-frame deletions; 2 substitution
- Prediction scores: 408 variants have prediction scores (60% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, severe acute respiratory syndrome, neoplasm, myelofibrosis, small cell lung carcinoma, acute lymphoblastic leukemia, acute myeloid leukemia, B-cell chronic lymphocytic leukemia, Thrombocytopenia, melanoma, chronic myelogenous leukemia, BCR-ABL1 positive, hereditary breast ovarian cancer syndrome.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 2 post-translational modification sites.
- Structural context: 42 variants have structural context.
- PTM context: 5 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 BCL2L1 variants
Examples include S2A, S2C, S2F, Q3R, Q3H, Q3L, Q3K, S4I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2A (p.Ser2Ala), gnomAD rs2061647075, REVEL 0.16, CADD 23.00
- S2C (p.Ser2Cys), Ensembl rs2122881027
- S2F (p.Ser2Phe), gnomAD 20-31722214-G-A, REVEL 0.28, MetaLR 0.04
- Q3R (p.Gln3Arg), TOPMed rs2061647005, gnomAD rs2061647005, REVEL 0.06, CADD 21.50
- Q3H (p.Gln3His), gnomAD 20-31722210-C-A, REVEL 0.04, MetaLR 0.01
- Q3L (p.Gln3Leu), gnomAD 20-31722211-T-A, REVEL 0.07, MetaLR 0.01
- Q3K (p.Gln3Lys), gnomAD 20-31722212-G-T, REVEL 0.04, MetaLR 0.01
- S4I (p.Ser4Ile), gnomAD 20-31722208-C-A, REVEL 0.16, MetaLR 0.05
- S4G (p.Ser4Gly), gnomAD 20-31722209-T-C, REVEL 0.12, MetaLR 0.03
- N5N (p.Asn5Asn), gnomAD 20-31722204-G-A, CADD 19.40
- N5S (p.Asn5Ser), gnomAD 20-31722205-T-C, REVEL 0.20, MetaLR 0.03
- R6G (p.Arg6Gly), ESP rs373119323, ExAC rs373119323, gnomAD rs373119323, REVEL 0.23, CADD 26.30
- R6L (p.Arg6Leu), 1000Genomes rs148274815, ESP rs148274815, ExAC rs148274815, TOPMed rs148274815, REVEL 0.36, CADD 25.50
- R6P (p.Arg6Pro), 1000Genomes rs148274815, ESP rs148274815, ExAC rs148274815, TOPMed rs148274815, REVEL 0.43, CADD 29.90
- R6Q (p.Arg6Gln), 1000Genomes rs148274815, ESP rs148274815, ExAC rs148274815, TOPMed rs148274815, REVEL 0.34, CADD 29.50
- R6W (p.Arg6Trp), ESP rs373119323, ExAC rs373119323, gnomAD rs373119323, REVEL 0.27, CADD 25.50
- R6R (p.Arg6Arg), gnomAD 20-31722203-G-T, CADD 18.90
- E7K (p.Glu7Lys), gnomAD rs1320914743, REVEL 0.36, CADD 27.30
- L8L (p.Leu8Leu), gnomAD 20-31722195-C-A, CADD 18.90
- L8P (p.Leu8Pro), gnomAD 20-31722196-A-G, REVEL 0.51, CADD 31.00
- V9L (p.Val9Leu), TOPMed rs2061646533, gnomAD rs2061646533, REVEL 0.33, CADD 26.10
- V9V (p.Val9Val), rs2061646474, gnomAD 20-31722192-C-T, CADD 18.80
- V10D (p.Val10Asp), Ensembl rs2122880730
- V10F (p.Val10Phe), ExAC rs752292810, TOPMed rs752292810, gnomAD rs752292810, REVEL 0.15, CADD 22.40
- V10G (p.Val10Gly), Ensembl rs2122880730
- V10I (p.Val10Ile), ExAC rs752292810, TOPMed rs752292810, gnomAD rs752292810, REVEL 0.06, CADD 20.20
- V10A (p.Val10Ala), gnomAD 20-31722190-A-G, REVEL 0.14, CADD 24.20
- D11E (p.Asp11Glu), gnomAD 20-31722186-G-T, REVEL 0.13, CADD 22.50
- D11Y (p.Asp11Tyr), gnomAD 20-31722188-C-A, REVEL 0.17, CADD 22.80
- F12S (p.Phe12Ser), rs1452829095, gnomAD 20-31722182-GAA-G, CADD 28.00
- F12L (p.Phe12Leu), gnomAD 20-31722185-A-G, REVEL 0.41, CADD 28.90
- L13L (p.Leu13Leu), rs11550474, gnomAD 20-31722180-G-A, CADD 17.70
- S14Y (p.Ser14Tyr), gnomAD 20-31722178-G-T, REVEL 0.21, CADD 26.70
- S14F (p.Ser14Phe), gnomAD 20-31722178-G-A, REVEL 0.21, CADD 27.10
- S14A (p.Ser14Ala), gnomAD 20-31722179-A-C, REVEL 0.09, CADD 23.70
- Y15H (p.Tyr15His), ExAC rs759603556, gnomAD rs759603556, REVEL 0.31, CADD 27.90
- Y15* (p.Tyr15Ter), gnomAD 20-31722174-G-T, CADD 35.00
- Y15Y (p.Tyr15Tyr), gnomAD 20-31722174-G-A, CADD 19.00
- Y15C (p.Tyr15Cys), gnomAD 20-31722175-T-C, REVEL 0.44, CADD 29.60
- K16N (p.Lys16Asn), Ensembl rs2122880540
- K16R (p.Lys16Arg), gnomAD rs1272422177, REVEL 0.33, CADD 28.40
- K16K (p.Lys16Lys), gnomAD 20-31722171-C-T, CADD 20.30
- L17I (p.Leu17Ile), gnomAD 20-31722170-G-T, REVEL 0.36, CADD 27.50
- S18C (p.Ser18Cys), Ensembl rs2122880490
- S18F (p.Ser18Phe), cosmic curated COSV56966, REVEL 0.38, CADD 29.20
- S18S (p.Ser18Ser), gnomAD 20-31722165-G-A, CADD 18.40
- Q19H (p.Gln19His), Ensembl rs2122880467, REVEL 0.23, CADD 25.00
- Q19Q (p.Gln19Gln), gnomAD 20-31722162-C-T, CADD 19.60
- Q19R (p.Gln19Arg), gnomAD 20-31722163-T-C, REVEL 0.42, CADD 27.70
- Q19P (p.Gln19Pro), gnomAD 20-31722163-T-G, REVEL 0.51, CADD 28.50
- Q19K (p.Gln19Lys), gnomAD 20-31722164-G-T, REVEL 0.26, CADD 26.60
- Q19* (p.Gln19Ter), gnomAD 20-31722164-G-A, CADD 36.00
- K20K (p.Lys20Lys), gnomAD 20-31722159-T-C, CADD 20.30
- K20E (p.Lys20Glu), gnomAD 20-31722161-T-C, REVEL 0.16, CADD 26.60
- G21E (p.Gly21Glu), Ensembl rs2122880442
- G21G (p.Gly21Gly), rs1383470049, gnomAD 20-31722156-T-A, CADD 20.80
- G21V (p.Gly21Val), gnomAD 20-31722157-C-A, REVEL 0.34, CADD 26.60
- G21* (p.Gly21Ter), gnomAD 20-31722158-C-A, CADD 36.00
- Y22C (p.Tyr22Cys), TOPMed rs1296172344, REVEL 0.38, CADD 30.00, Uncertain significance, not specified
- Y22* (p.Tyr22Ter), gnomAD 20-31722153-G-T, CADD 36.00
- Y22Y (p.Tyr22Tyr), rs2122880359, gnomAD 20-31722153-G-A, CADD 20.80
- Y22H (p.Tyr22His), gnomAD 20-31722155-A-G, REVEL 0.12, CADD 22.90
- S23N (p.Ser23Asn), Ensembl rs2122880340, REVEL 0.04, CADD 19.00
- S23R (p.Ser23Arg), Ensembl rs2122880303, REVEL 0.04, CADD 21.10
- S23S (p.Ser23Ser), rs2122880303, gnomAD 20-31722150-G-A, CADD 19.00
- S23I (p.Ser23Ile), gnomAD 20-31722151-C-A, REVEL 0.05, CADD 21.80
- W24* (p.Trp24Ter), Ensembl rs2122880273, CADD 36.00
- W24C (p.Trp24Cys), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10030, Variant assessed as somatic; moderate impact.
- W24L (p.Trp24Leu), gnomAD 20-31722148-C-A, REVEL 0.23, CADD 22.80
- S25N (p.Ser25Asn), NCI-TCGA TCGA novel, REVEL 0.06, CADD 21.20, Variant assessed as somatic; moderate impact.
- S25S (p.Ser25Ser), gnomAD 20-31722144-A-G, CADD 20.50
- S25R (p.Ser25Arg), gnomAD 20-31722144-A-T, REVEL 0.10, CADD 22.40
- S25I (p.Ser25Ile), gnomAD 20-31722145-C-A, REVEL 0.13, CADD 22.80
- S25C (p.Ser25Cys), gnomAD 20-31722146-T-A, REVEL 0.12, CADD 24.40
- S25G (p.Ser25Gly), gnomAD 20-31722146-T-C, REVEL 0.08, CADD 24.30
- Q26K (p.Gln26Lys), cosmic curated COSV56969, REVEL 0.09, CADD 20.40
- Q26R (p.Gln26Arg), Ensembl rs2061645892, REVEL 0.08, CADD 21.80
- Q26H (p.Gln26His), gnomAD 20-31722141-C-A, REVEL 0.04, CADD 18.10
- F27* (p.Phe27Ter), cosmic curated COSV56967
- F27I (p.Phe27Ile), Ensembl rs2122880226, REVEL 0.07, CADD 22.60
- F27S (p.Phe27Ser), gnomAD 20-31722139-A-G, REVEL 0.07, CADD 25.20
- S28R (p.Ser28Arg), ExAC rs753681012, TOPMed rs753681012, gnomAD rs753681012
- S28S (p.Ser28Ser), gnomAD 20-31722135-A-G, CADD 17.30
- S28I (p.Ser28Ile), gnomAD 20-31722136-C-A, REVEL 0.04, CADD 19.70
- D29E (p.Asp29Glu), gnomAD rs1293982067
- D29H (p.Asp29His), gnomAD rs1325938235
- D29N (p.Asp29Asn), gnomAD rs1325938235, REVEL 0.05, CADD 21.90
- D29G (p.Asp29Gly), gnomAD 20-31722133-T-C, REVEL 0.07, CADD 22.60
- D29Y (p.Asp29Tyr), gnomAD 20-31722134-C-A, REVEL 0.10, CADD 22.60
- V30V (p.Val30Val), gnomAD 20-31722129-C-A, CADD 18.50
- V30L (p.Val30Leu), gnomAD 20-31722131-C-A, REVEL 0.04, CADD 22.00
- V30M (p.Val30Met), gnomAD 20-31722131-C-T, REVEL 0.05, CADD 22.70
- E31K (p.Glu31Lys), Ensembl rs2122880102
- E31E (p.Glu31Glu), rs1409340420, gnomAD 20-31722126-T-C, CADD 18.00
- E31A (p.Glu31Ala), gnomAD 20-31722127-T-G, REVEL 0.07, CADD 23.20
- E31* (p.Glu31Ter), gnomAD 20-31722128-C-A, CADD 36.00
- E32D (p.Glu32Asp), ExAC rs760750448, TOPMed rs760750448, gnomAD rs760750448, cosmic curated COSV56969, REVEL 0.07, CADD 18.40
- E32G (p.Glu32Gly), ExAC rs766199813, gnomAD rs766199813
- E32K (p.Glu32Lys), TOPMed rs2061645641
- E32R (p.Glu32Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- N33K (p.Asn33Lys), Ensembl rs2122879974, REVEL 0.01, CADD 20.30
- N33del (p.Asn33del), rs752845959, gnomAD 20-31722118-CTGT-, CADD 19.80
- N33N (p.Asn33Asn), gnomAD 20-31722120-G-A, CADD 17.90
- R34K (p.Arg34Lys), ExAC rs773505559, TOPMed rs773505559, REVEL 0.04, CADD 22.90
- R34M (p.Arg34Met), cosmic curated COSV56968, REVEL 0.18, CADD 26.60
- R34S (p.Arg34Ser), Ensembl rs2122879900, REVEL 0.10, CADD 22.60
- R34T (p.Arg34Thr), ExAC rs773505559, TOPMed rs773505559, REVEL 0.16, CADD 22.70
- R34G (p.Arg34Gly), gnomAD 20-31722119-T-C, REVEL 0.12, CADD 24.40
- T35T (p.Thr35Thr), gnomAD 20-31722114-A-G, CADD 20.20
- T35N (p.Thr35Asn), gnomAD 20-31722115-G-T, REVEL 0.09, CADD 22.60
- T35I (p.Thr35Ile), gnomAD 20-31722115-G-A, REVEL 0.24, CADD 24.30
- T35S (p.Thr35Ser), gnomAD 20-31722116-T-A, REVEL 0.11, CADD 22.80
- E36Q (p.Glu36Gln), cosmic curated COSV10588, Ensembl rs2122879873
- E36E (p.Glu36Glu), rs772005799, gnomAD 20-31722111-C-T, CADD 17.30
- E36G (p.Glu36Gly), gnomAD 20-31722112-T-C, REVEL 0.05, CADD 23.10
- E36* (p.Glu36Ter), gnomAD 20-31722113-C-A, CADD 36.00
- A37D (p.Ala37Asp), gnomAD rs1175487979, REVEL 0.04, CADD 19.40
- A37T (p.Ala37Thr), NCI-TCGA TCGA novel, REVEL 0.07, CADD 20.90, Variant assessed as somatic; moderate impact.
- A37V (p.Ala37Val), gnomAD rs1175487979
- A37A (p.Ala37Ala), gnomAD 20-31722108-G-T, CADD 19.60
- A37S (p.Ala37Ser), gnomAD 20-31722110-C-A, REVEL 0.06, CADD 19.50
- P38A (p.Pro38Ala), TOPMed rs1410318896, gnomAD rs1410318896, REVEL 0.05, CADD 17.00
- P38L (p.Pro38Leu), TOPMed rs2061645189
- P38S (p.Pro38Ser), TOPMed rs1410318896, gnomAD rs1410318896, REVEL 0.06, CADD 17.20
- P38Q (p.Pro38Gln), gnomAD 20-31722105-TG-T, CADD 30.00
- P38T (p.Pro38Thr), gnomAD 20-31722107-G-T, REVEL 0.06, CADD 16.90
- E39K (p.Glu39Lys), cosmic curated COSV10030, Ensembl rs1379893911
- E39Q (p.Glu39Gln), cosmic curated COSV10646
- E39V (p.Glu39Val), cosmic curated COSV56966
- E39E (p.Glu39Glu), rs761851595, gnomAD 20-31722102-T-C, CADD 20.30
- G40E (p.Gly40Glu), ExAC rs769141052, TOPMed rs769141052, gnomAD rs769141052, REVEL 0.06, CADD 16.50
- G40R (p.Gly40Arg), ExAC rs774465563, TOPMed rs774465563, gnomAD rs774465563, REVEL 0.07, CADD 21.80
- G40G (p.Gly40Gly), gnomAD 20-31722099-C-A, CADD 13.80
- G40V (p.Gly40Val), gnomAD 20-31722100-C-A, REVEL 0.05, CADD 16.80
- T41I (p.Thr41Ile), cosmic curated COSV10610, Ensembl rs2122879602
- T41S (p.Thr41Ser), Ensembl rs2122879602
- T41T (p.Thr41Thr), gnomAD 20-31722096-A-G, CADD 18.40
- T41N (p.Thr41Asn), gnomAD 20-31722097-G-T, REVEL 0.05, CADD 17.70
- T41L (p.Thr41Leu), gnomAD 20-31722101-CT-C, CADD 25.40
- E42K (p.Glu42Lys), Ensembl rs2122879585
- E42E (p.Glu42Glu), rs1237575319, gnomAD 20-31722093-T-C, CADD 16.80
- E42G (p.Glu42Gly), gnomAD 20-31722094-T-C, REVEL 0.03, CADD 22.80
- E42* (p.Glu42Ter), gnomAD 20-31722095-C-A, CADD 35.00
- S43L (p.Ser43Leu), ESP rs145910874, ExAC rs145910874, TOPMed rs145910874, gnomAD rs145910874, REVEL 0.06, CADD 22.80
- S43W (p.Ser43Trp), ESP rs145910874, ExAC rs145910874, TOPMed rs145910874, gnomAD rs145910874, REVEL 0.11, CADD 27.30
- S43S (p.Ser43Ser), rs11550476, gnomAD 20-31722090-C-A, CADD 14.70
- S43* (p.Ser43Ter), gnomAD 20-31722091-G-T, CADD 36.00
- E44D (p.Glu44Asp), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10030, ExAC rs770213331, gnomAD rs770213331, REVEL 0.03, CADD 15.60, Variant assessed as somatic; moderate impact.
- E44G (p.Glu44Gly), Ensembl rs2061644591, REVEL 0.06, CADD 23.40
- E44Q (p.Glu44Gln), Ensembl rs2122879466
- M45L (p.Met45Leu), Ensembl rs2061644500
- M45R (p.Met45Arg), Ensembl rs2122879368
- E46R (p.Glu46Arg), gnomAD 20-31722082-TC-T, CADD 29.50
- E46K (p.Glu46Lys), gnomAD 20-31722083-C-T, REVEL 0.09, CADD 22.80
- T47I (p.Thr47Ile), cosmic curated COSV10030, Ensembl rs2122879305, REVEL 0.05, CADD 19.90
- T47P (p.Thr47Pro), Ensembl rs1600328561
- T47S (p.Thr47Ser), Ensembl rs1600328561
- T47T (p.Thr47Thr), rs2122879280, gnomAD 20-31722078-G-A, CADD 18.00
- T47N (p.Thr47Asn), gnomAD 20-31722079-G-T, REVEL 0.03, CADD 18.10
- P48S (p.Pro48Ser), ESP rs376431497, ExAC rs376431497, TOPMed rs376431497, gnomAD rs376431497, REVEL 0.08, CADD 21.80
- P48H (p.Pro48His), gnomAD 20-31722076-G-T, REVEL 0.11, CADD 23.10
- P48T (p.Pro48Thr), gnomAD 20-31722077-G-T, REVEL 0.07, CADD 22.50
- S49N (p.Ser49Asn), TOPMed rs2061644325, REVEL 0.17, CADD 22.60
- S49V (p.Ser49Val), rs1308464449, gnomAD 20-31722074-TG-T, CADD 27.20
- A50G (p.Ala50Gly), Ensembl rs2122879140
- A50T (p.Ala50Thr), Ensembl rs2122879181
- A50V (p.Ala50Val), NCI-TCGA Cosmic COSV5696, cosmic curated COSV56967, Ensembl rs2122879140, Variant assessed as somatic; moderate impact.
- A50D (p.Ala50Asp), gnomAD 20-31722070-G-T, REVEL 0.07, CADD 22.50
- I51M (p.Ile51Met), ESP rs368700316, REVEL 0.05, CADD 20.00
- I51N (p.Ile51Asn), gnomAD rs1213362070
- I51T (p.Ile51Thr), gnomAD rs1213362070
- I51V (p.Ile51Val), ExAC rs777448557, gnomAD rs777448557, REVEL 0.04, CADD 17.40
- I51I (p.Ile51Ile), gnomAD 20-31722066-G-T, CADD 18.80
- N52S (p.Asn52Ser), cosmic curated COSV10966, TOPMed rs1187252281, gnomAD rs1187252281, REVEL 0.10, CADD 22.30
- G53C (p.Gly53Cys), gnomAD rs1339243134, REVEL 0.23, CADD 27.20
- G53D (p.Gly53Asp), ExAC rs758032919, TOPMed rs758032919, gnomAD rs758032919, REVEL 0.23, CADD 24.20
- G53G (p.Gly53Gly), gnomAD 20-31722060-G-T, CADD 19.40
- G53V (p.Gly53Val), gnomAD 20-31722061-C-A, REVEL 0.25, CADD 26.00
- N54S (p.Asn54Ser), Ensembl rs980933909
- N54T (p.Asn54Thr), Ensembl rs980933909
Public BCL2L1 analysis runs
- BCL2L1 analysis run — BCL2L1 (675 variants) — completed 2026-08-19