BCL2 (Apoptosis regulator Bcl-2) variants and mutations
BCL2 (also known as Apoptosis regulator Bcl-2) is a human protein-coding gene encoding an apoptosis regulator Bcl-2 protein. It prevents mitochondrial outer-membrane permeabilization by binding pro-apoptotic BCL-2-family proteins and thereby prolongs cell survival. The t(14;18) translocation drives persistent expression in follicular lymphoma, and BCL2 dependence is therapeutically targetable in several blood cancers. This analysis covers 937 BCL2 variants and mutations. Of these, 68% have computational variant effect predictions. Disease context includes B-cell chronic lymphocytic leukemia, neoplasm, and diffuse large B-cell lymphoma. Example BCL2 variants include M1?, A2P, and A2S.
Variant analysis overview
- Gene: BCL2
- Protein: Apoptosis regulator Bcl-2
- UniProt accession: P10415
- Organism: Homo sapiens
- Variants analyzed: 937
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 688 unspecified-consequence records; 3 stop lost; 136 synonymous variants; 93 missense variants; 1 stop retained variant; 7 frameshift variants; 1 protein altering variant; 2 in-frame insertions; 5 in-frame deletions; 1 stop-gained variants
- Prediction scores: 635 variants have prediction scores (68% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: B-cell chronic lymphocytic leukemia, neoplasm, diffuse large B-cell lymphoma, neurodegenerative disease, acute myeloid leukemia, plasma cell myeloma, prostate carcinoma, type 2 diabetes mellitus, lymphoid leukemia, lymphoid neoplasm, diabetes mellitus, neoplasm of mature B-cells.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 3 post-translational modification sites.
- Structural context: 40 variants have structural context.
- PTM context: 17 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 BCL2 variants
Examples include M1?, A2P, A2S, A2T, A2V, H3D, H3L, H3N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV10520
- A2P (p.Ala2Pro), cosmic curated COSV61374
- A2S (p.Ala2Ser), cosmic curated COSV61381, MetaLR 0.08, MetaSVM -1.07
- A2T (p.Ala2Thr), cosmic curated COSV61374, REVEL 0.15, MetaLR 0.10
- A2V (p.Ala2Val), rs1273284492, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10038, gnomAD rs1273284492, REVEL 0.12, MetaLR 0.08, Variant assessed as somatic; moderate impact.
- H3D (p.His3Asp), NCI-TCGA Cosmic COSV6139, cosmic curated COSV61390, Variant assessed as somatic; moderate impact.
- H3L (p.His3Leu), cosmic curated COSV10520
- H3N (p.His3Asn), cosmic curated COSV10520
- H3Q (p.His3Gln), cosmic curated COSV61384, MetaLR 0.03, MetaSVM -1.05
- H3R (p.His3Arg), 1000Genomes rs557714365, ExAC rs557714365, gnomAD rs557714365, REVEL 0.07, MetaLR 0.03
- A4G (p.Ala4Gly), cosmic curated COSV61376, MetaLR 0.02, MetaSVM -1.07
- A4P (p.Ala4Pro), NCI-TCGA Cosmic COSV6137, NCI-TCGA Cosmic COSV6138, cosmic curated COSV61381, REVEL 0.03, MetaLR 0.01, Variant assessed as somatic; moderate impact.
- A4S (p.Ala4Ser), cosmic curated COSV10520, ExAC rs768498963, gnomAD rs768498963, REVEL 0.04, MetaLR 0.02
- A4T (p.Ala4Thr), cosmic curated COSV61371, ExAC rs768498963, gnomAD rs768498963, REVEL 0.04, MetaLR 0.02
- A4V (p.Ala4Val), cosmic curated COSV61375, REVEL 0.07, MetaLR 0.02
- G5E (p.Gly5Glu), cosmic curated COSV61382
- G5R (p.Gly5Arg), cosmic curated COSV10520
- G5V (p.Gly5Val), cosmic curated COSV61372, MetaLR 0.05, MetaSVM -1.12
- R6* (p.Arg6Ter), Ensembl rs2144326345
- R6G (p.Arg6Gly), cosmic curated COSV61375
- R6I (p.Arg6Ile), cosmic curated COSV61383
- R6K (p.Arg6Lys), cosmic curated COSV10520, Ensembl rs2144326335
- R6S (p.Arg6Ser), cosmic curated COSV10520
- R6T (p.Arg6Thr), cosmic curated COSV61374, MetaLR 0.01, MetaSVM -0.90
- T7A (p.Thr7Ala), cosmic curated COSV61376
- T7I (p.Thr7Ile), NCI-TCGA Cosmic COSV6137, cosmic curated COSV61373, NCI-TCGA Cosmic COSV6138, Variant assessed as somatic; moderate impact.
- T7K (p.Thr7Lys), cosmic curated COSV61383
- T7P (p.Thr7Pro), cosmic curated COSV61381
- T7R (p.Thr7Arg), cosmic curated COSV61374, Ensembl rs2144326312
- T7S (p.Thr7Ser), UniProt VAR 000827
- G8A (p.Gly8Ala), cosmic curated COSV61371, REVEL 0.12, MetaLR 0.03
- G8E (p.Gly8Glu), cosmic curated COSV61377, ExAC rs775404824, gnomAD rs775404824, cosmic curated COSV61391, REVEL 0.16, MetaLR 0.03
- G8R (p.Gly8Arg), cosmic curated COSV10520, Ensembl rs2144326271
- G8W (p.Gly8Trp), cosmic curated COSV10520
- Y9* (p.Tyr9Ter), cosmic curated COSV10648
- Y9C (p.Tyr9Cys), cosmic curated COSV10520, REVEL 0.24, MetaLR 0.05
- Y9D (p.Tyr9Asp), Ensembl rs2144326250
- Y9F (p.Tyr9Phe), cosmic curated COSV61383
- Y9H (p.Tyr9His), cosmic curated COSV61382, REVEL 0.28, MetaLR 0.04
- Y9S (p.Tyr9Ser), cosmic curated COSV10520, MetaLR 0.05, MetaSVM -1.17
- Y9Y (p.Tyr9Tyr), rs2144326239, gnomAD 18-63318640-G-A, CADD 0.96
- D10E (p.Asp10Glu), Ensembl rs2144326215
- D10N (p.Asp10Asn), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10038, Ensembl rs2144326228, MetaLR 0.02, MetaSVM -1.11, Variant assessed as somatic; moderate impact.
- D10V (p.Asp10Val), gnomAD 18-63318637-AT-A, CADD 26.00
- N11H (p.Asn11His), cosmic curated COSV61379
- N11K (p.Asn11Lys), cosmic curated COSV61385, Ensembl rs2144326188
- N11S (p.Asn11Ser), ExAC rs769588208, REVEL 0.22, MetaLR 0.03
- N11Y (p.Asn11Tyr), cosmic curated COSV61385, TOPMed rs1765676229
- N11N (p.Asn11Asn), rs1914828844, gnomAD 18-63158091-A-G, CADD 3.95
- R12G (p.Arg12Gly), TOPMed rs960653284
- R12P (p.Arg12Pro), Ensembl rs2144326150
- R12Q (p.Arg12Gln), Ensembl rs2144326150, MetaLR 0.05, MetaSVM -1.19
- R12W (p.Arg12Trp), cosmic curated COSV61392, REVEL 0.44, MetaLR 0.05
- R12R (p.Arg12Arg), rs1414251123, gnomAD 18-63318631-C-T, CADD 9.94
- E13D (p.Glu13Asp), cosmic curated COSV61372, Uncertain significance, Neoplasm
- E13Q (p.Glu13Gln), Ensembl rs2144326111, MetaLR 0.02, MetaSVM -1.00
- E13G (p.Glu13Gly), gnomAD 18-63161847-T-C, CADD 23.10, SIFT 0.02
- E13K (p.Glu13Lys), gnomAD 18-63318630-C-T, REVEL 0.15, MetaLR 0.04
- I14L (p.Ile14Leu), cosmic curated COSV61379
- I14M (p.Ile14Met), cosmic curated COSV61393
- I14R (p.Ile14Arg), 1000Genomes rs2144326092
- I14T (p.Ile14Thr), 1000Genomes rs2144326092
- I14I (p.Ile14Ile), rs2144326085, gnomAD 18-63318625-T-A, CADD 10.60
- V15G (p.Val15Gly), Ensembl rs2144326057
- V15L (p.Val15Leu), ExAC rs745851862, gnomAD rs745851862
- V15M (p.Val15Met), ExAC rs745851862, gnomAD rs745851862
- V15I (p.Val15Ile), rs1273752303, gnomAD 18-63158084-C-T, CADD 4.67, SIFT 0.15
- V15V (p.Val15Val), gnomAD 18-63318622-C-T, CADD 12.90
- M16I (p.Met16Ile), TOPMed rs776360417, gnomAD rs776360417, REVEL 0.04, MetaLR 0.01
- M16K (p.Met16Lys), cosmic curated COSV61378
- M16L (p.Met16Leu), cosmic curated COSV61380
- M16R (p.Met16Arg), cosmic curated COSV61373, Ensembl rs2144326044
- M16T (p.Met16Thr), cosmic curated COSV10520, REVEL 0.08, MetaLR 0.01
- M16V (p.Met16Val), cosmic curated COSV61396, MetaLR 0.01, MetaSVM -1.02
- K17E (p.Lys17Glu), cosmic curated COSV61389, ExAC rs780634396, TOPMed rs780634396, gnomAD rs780634396, REVEL 0.12, MetaLR 0.03
- K17M (p.Lys17Met), NCI-TCGA Cosmic COSV6137, cosmic curated COSV61379, MetaLR 0.04, MetaSVM -1.16, Variant assessed as somatic; moderate impact.
- K17N (p.Lys17Asn), cosmic curated COSV61372, cosmic curated COSV61388, 1000Genomes rs565741123, ExAC rs565741123, REVEL 0.11, MetaLR 0.01, Uncertain significance, Neoplasm
- K17K (p.Lys17Lys), rs565741123, gnomAD 18-63318616-C-T, CADD 12.50
- K17T (p.Lys17Thr), gnomAD 18-63318617-T-G, REVEL 0.13, MetaLR 0.03
- Y18D (p.Tyr18Asp), Ensembl rs2144326007
- Y18F (p.Tyr18Phe), cosmic curated COSV10441
- I19L (p.Ile19Leu), cosmic curated COSV10942, ExAC rs746600883, TOPMed rs746600883, gnomAD rs746600883, REVEL 0.14, MetaLR 0.01
- I19M (p.Ile19Met), cosmic curated COSV10520, MetaLR 0.03, MetaSVM -1.06
- I19I (p.Ile19Ile), rs1476761924, gnomAD 18-63318610-G-A, CADD 14.20
- H20N (p.His20Asn), ExAC rs777401949, TOPMed rs777401949, gnomAD rs777401949, REVEL 0.11, MetaLR 0.03
- H20Q (p.His20Gln), cosmic curated COSV61372, 1000Genomes rs758123306, ExAC rs758123306, TOPMed rs758123306, REVEL 0.14, MetaLR 0.02
- H20R (p.His20Arg), cosmic curated COSV10520, REVEL 0.12, MetaLR 0.02
- Y21C (p.Tyr21Cys), cosmic curated COSV61383
- Y21H (p.Tyr21His), cosmic curated COSV61396
- Y21S (p.Tyr21Ser), cosmic curated COSV61381, MetaLR 0.05, MetaSVM -1.17
- K22* (p.Lys22Ter), cosmic curated COSV61384
- K22N (p.Lys22Asn), cosmic curated COSV10567
- K22R (p.Lys22Arg), cosmic curated COSV61380
- L23M (p.Leu23Met), gnomAD rs1441603213, REVEL 0.37, MetaLR 0.06
- L23V (p.Leu23Val), cosmic curated COSV10814, gnomAD rs1441603213
- L23L (p.Leu23Leu), rs1178177633, gnomAD 18-63318598-C-G, CADD 14.20
- S24A (p.Ser24Ala), Ensembl rs2144325928
- S24L (p.Ser24Leu), rs1913587435, ClinGen CA402633160, ClinVar RCV004426281, TOPMed rs1913587435, AlphaMissense 0.47, MetaLR 0.02, Uncertain significance, not specified
- S24P (p.Ser24Pro), Ensembl rs2144325928
- S24T (p.Ser24Thr), Ensembl rs2144325928
- S24W (p.Ser24Trp), TOPMed rs1913587435, MetaLR 0.02, MetaSVM -1.04, Uncertain significance
- S24S (p.Ser24Ser), rs752978070, gnomAD 18-63318595-C-A, CADD 11.90
- Q25* (p.Gln25Ter), gnomAD rs1197724553
- Q25E (p.Gln25Glu), gnomAD rs1197724553, REVEL 0.22, MetaLR 0.04
- R26K (p.Arg26Lys), cosmic curated COSV10038, MetaLR 0.04, MetaSVM -1.17
- G27A (p.Gly27Ala), Ensembl rs2144325860
- G27D (p.Gly27Asp), cosmic curated COSV61378, Ensembl rs2144325860, MetaLR 0.04, MetaSVM -1.13
- G27S (p.Gly27Ser), ExAC rs779372254, gnomAD rs779372254, REVEL 0.41, MetaLR 0.04
- G27G (p.Gly27Gly), gnomAD 18-63318586-G-T, CADD 13.60
- G27V (p.Gly27Val), gnomAD 18-63318587-C-A, REVEL 0.47, MetaLR 0.05
- Y28* (p.Tyr28Ter), ExAC rs755397980, gnomAD rs755397980
- Y28F (p.Tyr28Phe), cosmic curated COSV61393
- Y28H (p.Tyr28His), rs1555711318, NCI-TCGA Cosmic COSV6138, cosmic curated COSV61382, Ensembl rs1555711318, REVEL 0.32, MetaLR 0.04, Variant assessed as somatic; moderate impact.
- Y28N (p.Tyr28Asn), cosmic curated COSV10465
- Y28S (p.Tyr28Ser), cosmic curated COSV10520, Ensembl rs2144325834, MetaLR 0.04, MetaSVM -1.18
- Y28Y (p.Tyr28Tyr), rs755397980, gnomAD 18-63318583-G-A, CADD 11.30
- E29* (p.Glu29Ter), cosmic curated COSV10737
- E29D (p.Glu29Asp), cosmic curated COSV10520, cosmic curated COSV61396
- E29G (p.Glu29Gly), Ensembl rs2144325802
- E29K (p.Glu29Lys), cosmic curated COSV61394, TOPMed rs1913586694, REVEL 0.09, MetaLR 0.02
- E29Q (p.Glu29Gln), cosmic curated COSV61372, TOPMed rs1913586694, MetaLR 0.01, MetaSVM -0.94
- E29E (p.Glu29Glu), gnomAD 18-63318580-C-T, CADD 8.63
- W30* (p.Trp30Ter), ExAC rs754418219, gnomAD rs754418219, CADD 35.00
- W30C (p.Trp30Cys), cosmic curated COSV61376, REVEL 0.28, MetaLR 0.03
- W30G (p.Trp30Gly), Ensembl rs2144325786
- W30L (p.Trp30Leu), Ensembl rs2144325773
- W30R (p.Trp30Arg), Ensembl rs2144325786, MetaLR 0.03, MetaSVM -1.18
- D31A (p.Asp31Ala), cosmic curated COSV61373
- D31E (p.Asp31Glu), cosmic curated COSV61372, cosmic curated COSV61394, Ensembl rs2144325742
- D31G (p.Asp31Gly), cosmic curated COSV61378
- D31H (p.Asp31His), cosmic curated COSV61373, ExAC rs766508625, TOPMed rs766508625, gnomAD rs766508625, REVEL 0.14, MetaLR 0.03
- D31N (p.Asp31Asn), rs766508625, NCI-TCGA Cosmic COSV6137, NCI-TCGA Cosmic COSV6138, cosmic curated COSV61383, REVEL 0.08, MetaLR 0.01, Variant assessed as somatic; moderate impact.
- D31Y (p.Asp31Tyr), cosmic curated COSV10648
- A32G (p.Ala32Gly), 1000Genomes rs546449806, ExAC rs546449806, TOPMed rs546449806, gnomAD rs546449806, REVEL 0.09, MetaLR 0.02
- A32P (p.Ala32Pro), ExAC rs760840889, gnomAD rs760840889, REVEL 0.16, MetaLR 0.02
- A32T (p.Ala32Thr), cosmic curated COSV61384
- A32V (p.Ala32Val), cosmic curated COSV61392, 1000Genomes rs546449806, ExAC rs546449806, TOPMed rs546449806, REVEL 0.12, MetaLR 0.01
- A32A (p.Ala32Ala), gnomAD 18-63318571-C-G, CADD 0.55
- A32E (p.Ala32Glu), gnomAD 18-63318572-G-T, REVEL 0.09, MetaLR 0.01
- A32S (p.Ala32Ser), gnomAD 18-63318573-C-A, REVEL 0.06, MetaLR 0.01
- G33E (p.Gly33Glu), cosmic curated COSV61372
- G33R (p.Gly33Arg), cosmic curated COSV10520, cosmic curated COSV61376, ExAC rs767612613, gnomAD rs767612613, REVEL 0.13, MetaLR 0.03
- D34A (p.Asp34Ala), cosmic curated COSV61399
- D34E (p.Asp34Glu), cosmic curated COSV61398, ExAC rs762137430, gnomAD rs762137430, REVEL 0.02, MetaLR 0.01
- D34G (p.Asp34Gly), NCI-TCGA Cosmic COSV6138, cosmic curated COSV61383, NCI-TCGA Cosmic COSV6139, TOPMed rs1913584883, MetaLR 0.01, MetaSVM -0.92, Variant assessed as somatic; moderate impact.
- D34H (p.Asp34His), cosmic curated COSV61379, 1000Genomes rs540701354, TOPMed rs540701354, gnomAD rs540701354, REVEL 0.12, MetaLR 0.01
- D34N (p.Asp34Asn), cosmic curated COSV61389, REVEL 0.06, MetaLR 0.01
- D34Y (p.Asp34Tyr), cosmic curated COSV10886, 1000Genomes rs540701354, TOPMed rs540701354, gnomAD rs540701354, REVEL 0.17, MetaLR 0.02
- D34D (p.Asp34Asp), rs762137430, gnomAD 18-63318565-A-G, CADD 3.01
- D34M (p.Asp34Met), rs759748900, gnomAD 18-63318567-CT-C, CADD 14.70
- V35E (p.Val35Glu), Ensembl rs2144325666
- V35G (p.Val35Gly), Ensembl rs2144325666
- V35L (p.Val35Leu), cosmic curated COSV10520
- V35M (p.Val35Met), cosmic curated COSV61383, ExAC rs775108608, TOPMed rs775108608, gnomAD rs775108608, REVEL 0.05, MetaLR 0.01
- V35V (p.Val35Val), gnomAD 18-63318562-C-G, CADD 5.72
- G36A (p.Gly36Ala), cosmic curated COSV10886
- G36D (p.Gly36Asp), cosmic curated COSV61372
- G36R (p.Gly36Arg), Ensembl rs2144325653
- G36G (p.Gly36Gly), rs1913584494, gnomAD 18-63318559-G-A, CADD 8.74
- G36V (p.Gly36Val), gnomAD 18-63318560-C-A, REVEL 0.04, MetaLR 0.01
- G36S (p.Gly36Ser), gnomAD 18-63318561-C-T, REVEL 0.03, MetaLR 0.01
- A37G (p.Ala37Gly), Ensembl rs2144325609, MetaLR 0.01, MetaSVM -0.95
- A37S (p.Ala37Ser), Ensembl rs1913584363, REVEL 0.03, MetaLR 0.01
- A37T (p.Ala37Thr), Ensembl rs1913584363, REVEL 0.04, MetaLR 0.01
- A37V (p.Ala37Val), cosmic curated COSV61377, Ensembl rs2144325609, REVEL 0.08, MetaLR 0.01
- A37A (p.Ala37Ala), rs769656259, gnomAD 18-63318556-G-T, CADD 3.91
- A38T (p.Ala38Thr), TOPMed rs1913584236, REVEL 0.05, MetaLR 0.01
- A38V (p.Ala38Val), Ensembl rs2144325571, REVEL 0.09, MetaLR 0.01
- A38A (p.Ala38Ala), rs1169270253, gnomAD 18-63318553-C-T, CADD 9.01
- A38E (p.Ala38Glu), gnomAD 18-63318554-G-T, REVEL 0.08, MetaLR 0.01
- P39A (p.Pro39Ala), cosmic curated COSV10520, REVEL 0.02, MetaLR 0.01
- P39L (p.Pro39Leu), cosmic curated COSV10520, gnomAD rs1224885133, REVEL 0.09, MetaLR 0.01
- P39S (p.Pro39Ser), Ensembl rs2144325540, MetaLR 0.02, MetaSVM -0.99
- P39R (p.Pro39Arg), rs1914828360, gnomAD 18-63158080-G-C, CADD 0.22, SIFT 0.17
- P39P (p.Pro39Pro), rs776558326, gnomAD 18-63318550-G-A, CADD 10.20
- P40L (p.Pro40Leu), ExAC rs770925898, gnomAD rs770925898, REVEL 0.04, MetaLR 0.01
- P40Q (p.Pro40Gln), ExAC rs770925898, gnomAD rs770925898, REVEL 0.07, MetaLR 0.01
- P40R (p.Pro40Arg), ExAC rs770925898, gnomAD rs770925898, REVEL 0.06, MetaLR 0.01
- P40P (p.Pro40Pro), gnomAD 18-63318547-C-A, CADD 0.85
- P40T (p.Pro40Thr), gnomAD 18-63318549-G-T, REVEL 0.07, MetaLR 0.01
Public BCL2 analysis runs
- BCL2 analysis run — BCL2 (937 variants) — completed 2026-08-18