BCL2L2 (Bcl-2-like protein 2) variants and mutations
BCL2L2 (also known as Bcl-2-like protein 2) is a human protein-coding gene encoding a bcl-2-like protein 2 protein. It promotes cell survival by binding pro-apoptotic BCL-2-family proteins and limiting mitochondrial apoptosis. Abnormal expression can help malignant or stressed cells resist death, although its clinical role is less dominant than that of BCL2 or BCL-XL. This analysis covers 553 BCL2L2 variants and mutations. Of these, 92% have computational variant effect predictions. Disease context includes neurodegenerative disease, neoplasm, and myelofibrosis. Example BCL2L2 variants include A2V, A2A, and T3N.
Variant analysis overview
- Gene: BCL2L2
- Protein: Bcl-2-like protein 2
- UniProt accession: Q92843
- Organism: Homo sapiens
- Variants analyzed: 553
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 182 unspecified-consequence records; 113 synonymous variants; 22 frameshift variants; 213 missense variants; 11 stop-gained variants; 3 in-frame deletions; 7 stop lost; 1 splice-region variants; 1 stop retained variant
- Prediction scores: 509 variants have prediction scores (92% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, neoplasm, myelofibrosis, small cell lung carcinoma, acute lymphoblastic leukemia, B-cell chronic lymphocytic leukemia, acute myeloid leukemia, lymphoblastic lymphoma, lymphoma, myelodysplastic syndrome, ovarian cancer, mantle cell lymphoma.
Protein structure and variant hotspots
- Protein features: 5 post-translational modification sites.
- PTM context: 9 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 BCL2L2 variants
Examples include A2V, A2A, T3N, T3P, T3T, P4Q, P4L, A5V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2V (p.Ala2Val), TOPMed rs1887328939, gnomAD rs1887328939, REVEL 0.22, CADD 26.10
- A2A (p.Ala2Ala), gnomAD 14-23307773-G-T, CADD 14.50
- T3N (p.Thr3Asn), gnomAD rs1170609821
- T3P (p.Thr3Pro), Ensembl rs1594977872
- T3T (p.Thr3Thr), gnomAD 14-23307776-C-T, CADD 13.60
- P4Q (p.Pro4Gln), gnomAD 14-23307774-AC-A, CADD 29.40
- P4L (p.Pro4Leu), gnomAD 14-23307778-C-T, REVEL 0.11, CADD 26.40
- A5V (p.Ala5Val), gnomAD 14-23307781-C-T, REVEL 0.09, CADD 23.40
- A5A (p.Ala5Ala), gnomAD 14-23307782-C-A, CADD 13.60
- S6L (p.Ser6Leu), cosmic curated COSV10605, TOPMed rs1414276111, gnomAD rs1414276111, REVEL 0.13, CADD 23.40
- S6W (p.Ser6Trp), TOPMed rs1414276111, gnomAD rs1414276111, REVEL 0.20, CADD 25.60
- S6T (p.Ser6Thr), gnomAD 14-23307783-T-A, REVEL 0.13, CADD 21.80
- S6S (p.Ser6Ser), gnomAD 14-23307785-G-C, CADD 0.76
- A7D (p.Ala7Asp), 1000Genomes rs536156541, TOPMed rs536156541, REVEL 0.06, CADD 23.20
- A7T (p.Ala7Thr), cosmic curated COSV51636, gnomAD rs1324030355
- A7A (p.Ala7Ala), rs145819636, gnomAD 14-23307788-C-T, CADD 13.60
- P8Q (p.Pro8Gln), gnomAD 14-23307786-GC-G, CADD 25.30
- P8P (p.Pro8Pro), rs781668542, gnomAD 14-23307791-A-G, CADD 15.00
- D9N (p.Asp9Asn), TOPMed rs1270507301, gnomAD rs1270507301, REVEL 0.17, CADD 24.70
- D9Y (p.Asp9Tyr), TOPMed rs1270507301, gnomAD rs1270507301, REVEL 0.34, CADD 29.50
- D9E (p.Asp9Glu), gnomAD 14-23307794-C-A, REVEL 0.15, CADD 23.20
- D9D (p.Asp9Asp), gnomAD 14-23307794-C-T, CADD 13.40
- T10A (p.Thr10Ala), gnomAD 14-23307795-A-G, REVEL 0.05, CADD 23.50
- T10K (p.Thr10Lys), gnomAD 14-23307796-C-A, REVEL 0.16, CADD 23.40
- R11L (p.Arg11Leu), ExAC rs750337260, TOPMed rs750337260, gnomAD rs750337260, REVEL 0.22, CADD 24.40
- R11Q (p.Arg11Gln), ExAC rs750337260, TOPMed rs750337260, gnomAD rs750337260, REVEL 0.13, CADD 24.50
- R11W (p.Arg11Trp), ExAC rs748717252, gnomAD rs748717252, REVEL 0.16, CADD 25.20
- R11G (p.Arg11Gly), gnomAD 14-23307797-AC-A, CADD 26.90
- A12S (p.Ala12Ser), ExAC rs778308004, TOPMed rs778308004, gnomAD rs778308004, REVEL 0.07, CADD 22.70
- A12T (p.Ala12Thr), ExAC rs778308004, TOPMed rs778308004, gnomAD rs778308004, REVEL 0.07, CADD 23.20
- A12G (p.Ala12Gly), gnomAD 14-23307802-C-G, REVEL 0.10, CADD 23.70
- A12D (p.Ala12Asp), gnomAD 14-23307802-C-A, REVEL 0.11, CADD 23.60
- L13L (p.Leu13Leu), rs528008535, gnomAD 14-23307804-C-T, CADD 12.50
- L13P (p.Leu13Pro), gnomAD 14-23307805-T-C, REVEL 0.36, CADD 28.30
- V14G (p.Val14Gly), gnomAD rs1335455103
- V14L (p.Val14Leu), gnomAD 14-23307807-G-T, REVEL 0.21, CADD 25.80
- A15G (p.Ala15Gly), TOPMed rs931181714
- A15S (p.Ala15Ser), ExAC rs749329745, TOPMed rs749329745, gnomAD rs749329745, REVEL 0.07, CADD 22.80
- A15T (p.Ala15Thr), cosmic curated COSV51636, ExAC rs749329745, TOPMed rs749329745, gnomAD rs749329745, REVEL 0.05, CADD 22.70
- A15E (p.Ala15Glu), gnomAD 14-23307811-C-A, REVEL 0.04, CADD 22.30
- A15V (p.Ala15Val), gnomAD 14-23307811-C-T, REVEL 0.08, CADD 20.20
- D16E (p.Asp16Glu), gnomAD 14-23307815-C-A, REVEL 0.16, CADD 23.60
- F17C (p.Phe17Cys), gnomAD 14-23307815-CTT-C, CADD 28.30
- F17S (p.Phe17Ser), gnomAD 14-23307817-T-C, REVEL 0.25, CADD 29.20
- F17F (p.Phe17Phe), rs1887335134, gnomAD 14-23307818-T-C, CADD 15.00
- V18L (p.Val18Leu), gnomAD 14-23307819-G-T, REVEL 0.21, CADD 22.00
- G19D (p.Gly19Asp), gnomAD 14-23307823-G-A, REVEL 0.13, CADD 24.10
- K21E (p.Lys21Glu), ExAC rs770982097, gnomAD rs770982097, REVEL 0.12, CADD 26.90
- K21R (p.Lys21Arg), gnomAD 14-23307829-A-G, REVEL 0.12, CADD 24.10
- L22M (p.Leu22Met), gnomAD 14-23307831-C-A, REVEL 0.29, CADD 25.60
- R23S (p.Arg23Ser), ExAC rs759748132, TOPMed rs759748132, gnomAD rs759748132, REVEL 0.22, CADD 21.30
- R23G (p.Arg23Gly), gnomAD 14-23307834-A-G, REVEL 0.14, CADD 23.20
- R23R (p.Arg23Arg), rs774492924, gnomAD 14-23307834-A-C, CADD 15.10
- R23W (p.Arg23Trp), gnomAD 14-23307834-A-T, REVEL 0.16, CADD 30.00
- R23M (p.Arg23Met), gnomAD 14-23307835-G-T, REVEL 0.20, CADD 27.10
- Q24K (p.Gln24Lys), gnomAD 14-23307837-C-A, REVEL 0.05, CADD 23.10
- Q24R (p.Gln24Arg), gnomAD 14-23307838-A-G, REVEL 0.09, CADD 23.60
- K25L (p.Lys25Leu), ExAC rs773694438
- K25T (p.Lys25Thr), ExAC rs768478219, TOPMed rs768478219, gnomAD rs768478219, REVEL 0.11, CADD 25.80
- K25R (p.Lys25Arg), gnomAD 14-23307839-GA-G, CADD 27.30
- K25E (p.Lys25Glu), gnomAD 14-23307840-A-G, REVEL 0.14, CADD 24.10
- K25Q (p.Lys25Gln), gnomAD 14-23307840-A-C, REVEL 0.08, CADD 23.90
- G26D (p.Gly26Asp), ExAC rs776387011, gnomAD rs776387011, REVEL 0.27, CADD 26.20
- G26C (p.Gly26Cys), gnomAD 14-23307843-G-T, REVEL 0.29, CADD 28.00
- G26V (p.Gly26Val), gnomAD 14-23307844-G-T, REVEL 0.32, CADD 23.90
- V28I (p.Val28Ile), ExAC rs761546942, gnomAD rs761546942, REVEL 0.03, CADD 22.00
- C29W (p.Cys29Trp), Ensembl rs1594977962
- C29Y (p.Cys29Tyr), gnomAD 14-23307853-G-A, REVEL 0.16, CADD 23.00
- G30R (p.Gly30Arg), Ensembl rs879162142, REVEL 0.10, CADD 27.50
- G30E (p.Gly30Glu), gnomAD 14-23307854-TG-T, CADD 32.00
- G30V (p.Gly30Val), gnomAD 14-23307856-G-T, REVEL 0.08, CADD 24.30
- A31T (p.Ala31Thr), gnomAD rs1324721950, REVEL 0.04, CADD 21.60
- A31S (p.Ala31Ser), gnomAD 14-23307858-G-T, REVEL 0.05, CADD 22.70
- G32D (p.Gly32Asp), TOPMed rs1566461548, REVEL 0.18, CADD 22.70
- G32R (p.Gly32Arg), TOPMed rs1476499405, gnomAD rs1476499405, REVEL 0.11, CADD 23.80
- G32S (p.Gly32Ser), gnomAD 14-23307861-G-A, REVEL 0.04, CADD 22.30
- G32G (p.Gly32Gly), gnomAD 14-23307863-C-T, CADD 11.80
- P33S (p.Pro33Ser), gnomAD rs1002769277, REVEL 0.05, CADD 22.80
- P33R (p.Pro33Arg), gnomAD 14-23307865-C-G, REVEL 0.12, CADD 23.20
- P33P (p.Pro33Pro), rs756008788, gnomAD 14-23307866-C-T, CADD 7.28
- G34R (p.Gly34Arg), rs773144952, ExAC rs773144952, TOPMed rs773144952, gnomAD rs773144952, REVEL 0.04, CADD 23.50, Variant assessed as somatic; moderate impact.
- G34W (p.Gly34Trp), NCI-TCGA Cosmic COSV5163, cosmic curated COSV51636, Variant assessed as somatic; moderate impact.
- G34V (p.Gly34Val), gnomAD 14-23307868-G-T, REVEL 0.07, CADD 25.20
- G34A (p.Gly34Ala), gnomAD 14-23307868-G-C, REVEL 0.04, CADD 21.50
- E35G (p.Glu35Gly), ExAC rs762429078, gnomAD rs762429078, REVEL 0.03, CADD 23.00
- E35R (p.Glu35Arg), gnomAD 14-23307862-GC-G, CADD 24.10
- E35E (p.Glu35Glu), rs2231300, gnomAD 14-23307872-G-A, CADD 10.30
- G36A (p.Gly36Ala), ExAC rs751213062, REVEL 0.03, CADD 21.90
- G36C (p.Gly36Cys), NCI-TCGA TCGA novel, REVEL 0.13, CADD 26.60, Variant assessed as somatic; moderate impact.
- G36S (p.Gly36Ser), TOPMed rs1291688709
- G36D (p.Gly36Asp), gnomAD 14-23307874-G-A, REVEL 0.06, CADD 23.60
- G36G (p.Gly36Gly), rs140247035, gnomAD 14-23307875-C-T, CADD 13.00
- P37S (p.Pro37Ser), TOPMed rs1351188968, gnomAD rs1351188968, REVEL 0.02, CADD 20.60
- A38A (p.Ala38Ala), gnomAD 14-23307881-A-C, CADD 11.30
- A39T (p.Ala39Thr), gnomAD 14-23307882-G-A, REVEL 0.03, CADD 16.20
- D40H (p.Asp40His), gnomAD rs1277383384, REVEL 0.04, CADD 23.50
- D40N (p.Asp40Asn), gnomAD 14-23307885-G-A, REVEL 0.04, CADD 22.20
- D40Y (p.Asp40Tyr), gnomAD 14-23307885-G-T, REVEL 0.06, CADD 23.80
- P41L (p.Pro41Leu), ESP rs372286720, ExAC rs372286720, TOPMed rs372286720, gnomAD rs372286720, REVEL 0.07, CADD 23.70
- P41R (p.Pro41Arg), ESP rs372286720, ExAC rs372286720, TOPMed rs372286720, gnomAD rs372286720, REVEL 0.07, CADD 23.60
- P41S (p.Pro41Ser), gnomAD 14-23307888-C-T, REVEL 0.03, CADD 23.00
- P41P (p.Pro41Pro), rs2231301, gnomAD 14-23307890-G-A, CADD 6.59
- L42P (p.Leu42Pro), gnomAD 14-23307892-T-C, REVEL 0.25, CADD 28.10
- H43N (p.His43Asn), TOPMed rs1887343568, REVEL 0.12, CADD 23.10
- H43P (p.His43Pro), 1000Genomes rs137944195, ESP rs137944195, ExAC rs137944195, TOPMed rs137944195
- H43R (p.His43Arg), 1000Genomes rs137944195, ESP rs137944195, ExAC rs137944195, TOPMed rs137944195, REVEL 0.10, CADD 23.20
- H43Y (p.His43Tyr), gnomAD 14-23307894-C-T, REVEL 0.07, CADD 23.10
- H43H (p.His43His), gnomAD 14-23307896-C-T, CADD 12.00
- Q44E (p.Gln44Glu), gnomAD 14-23307897-C-G, REVEL 0.06, CADD 19.80
- A45A (p.Ala45Ala), gnomAD 14-23307902-C-A, CADD 11.30
- M46I (p.Met46Ile), TOPMed rs1324750246, NCI-TCGA Cosmic COSV5163, cosmic curated COSV51636, Variant assessed as somatic; moderate impact.
- M46T (p.Met46Thr), cosmic curated COSV51635, gnomAD rs1887344145, REVEL 0.26, CADD 26.20
- R47Q (p.Arg47Gln), cosmic curated COSV51637, TOPMed rs1223928401, gnomAD rs1223928401, REVEL 0.34, CADD 31.00
- R47W (p.Arg47Trp), rs1355053032, NCI-TCGA Cosmic COSV9916, cosmic curated COSV99161, TOPMed rs1355053032, REVEL 0.33, CADD 26.30, Variant assessed as somatic; moderate impact.
- R47R (p.Arg47Arg), gnomAD 14-23307906-C-A, CADD 13.10
- R47L (p.Arg47Leu), gnomAD 14-23307907-G-T, REVEL 0.31, CADD 30.00
- A48T (p.Ala48Thr), TOPMed rs1444977614, gnomAD rs1444977614, REVEL 0.08, CADD 24.00
- A48V (p.Ala48Val), TOPMed rs1162370076
- G50A (p.Gly50Ala), ExAC rs757345605, gnomAD rs757345605, REVEL 0.20, CADD 23.70
- G50G (p.Gly50Gly), gnomAD 14-23307917-A-G, CADD 13.20
- D51E (p.Asp51Glu), Ensembl rs1887346163, REVEL 0.11, CADD 23.10
- D51N (p.Asp51Asn), Ensembl rs1361867382, REVEL 0.17, CADD 24.70
- D51D (p.Asp51Asp), gnomAD 14-23307920-T-C, CADD 13.90
- E52K (p.Glu52Lys), TOPMed rs1887346381
- E52E (p.Glu52Glu), rs1258701809, gnomAD 14-23307923-G-A, CADD 10.30
- F53L (p.Phe53Leu), 1000Genomes rs558357593, ExAC rs558357593, TOPMed rs558357593, gnomAD rs558357593, REVEL 0.11, CADD 15.80
- F53F (p.Phe53Phe), rs558357593, gnomAD 14-23307926-C-T, CADD 8.61
- E54Q (p.Glu54Gln), TOPMed rs1186442353, gnomAD rs1186442353, REVEL 0.24, CADD 27.20
- E54K (p.Glu54Lys), gnomAD 14-23307927-G-A, REVEL 0.30, CADD 29.90
- E54D (p.Glu54Asp), gnomAD 14-23307929-G-T, REVEL 0.13, CADD 23.50
- E54E (p.Glu54Glu), gnomAD 14-23307929-G-A, CADD 12.80
- T55S (p.Thr55Ser), gnomAD 14-23307931-C-G, REVEL 0.05, CADD 19.00
- R56C (p.Arg56Cys), TOPMed rs1367901961, gnomAD rs1367901961, REVEL 0.20, CADD 24.50
- R56H (p.Arg56His), ExAC rs746136637, TOPMed rs746136637, gnomAD rs746136637, REVEL 0.24, CADD 24.90
- R56P (p.Arg56Pro), gnomAD 14-23307934-G-C, REVEL 0.26, CADD 29.50
- F57L (p.Phe57Leu), gnomAD 14-23307938-C-G, REVEL 0.13, CADD 23.60
- R58G (p.Arg58Gly), ExAC rs772303364, TOPMed rs772303364, gnomAD rs772303364, REVEL 0.12, CADD 23.40
- R58Q (p.Arg58Gln), rs775649580, ClinGen CA7112424, cosmic curated COSV51636, ClinVar RCV004348416, REVEL 0.08, CADD 24.30, Uncertain significance, not specified
- R58W (p.Arg58Trp), ExAC rs772303364, TOPMed rs772303364, gnomAD rs772303364, REVEL 0.26, CADD 25.00
- R58R (p.Arg58Arg), gnomAD 14-23307941-G-A, CADD 13.10
- R59C (p.Arg59Cys), cosmic curated COSV51636, ESP rs377103042, ExAC rs377103042, TOPMed rs377103042, REVEL 0.11, CADD 23.50
- R59H (p.Arg59His), rs372109088, cosmic curated COSV51636, 1000Genomes rs372109088, ESP rs372109088, REVEL 0.11, CADD 23.40, Variant assessed as somatic; moderate impact.
- R59G (p.Arg59Gly), gnomAD 14-23307942-C-G, REVEL 0.11, CADD 24.10
- R59R (p.Arg59Arg), gnomAD 14-23307944-C-T, CADD 10.70
- T60I (p.Thr60Ile), Ensembl rs867739613, REVEL 0.04, CADD 22.80
- T60P (p.Thr60Pro), gnomAD 14-23307945-A-C, REVEL 0.10, CADD 24.30
- T60T (p.Thr60Thr), rs888194064, gnomAD 14-23307947-C-A, CADD 13.40
- F61L (p.Phe61Leu), TOPMed rs796896634, gnomAD rs796896634, REVEL 0.31, CADD 25.00
- F61F (p.Phe61Phe), rs1375862008, gnomAD 14-23307950-C-T, CADD 13.90
- S62F (p.Ser62Phe), gnomAD 14-23307952-C-T, REVEL 0.16, CADD 26.10
- D63N (p.Asp63Asn), Ensembl rs1887350034
- D63V (p.Asp63Val), rs1270964845, TOPMed rs1270964845, gnomAD rs1270964845, REVEL 0.38, CADD 28.40, Variant assessed as somatic; moderate impact.
- L64L (p.Leu64Leu), gnomAD 14-23307957-C-T, CADD 10.90
- A65E (p.Ala65Glu), ExAC rs773091533, TOPMed rs773091533, gnomAD rs773091533
- A65V (p.Ala65Val), ExAC rs773091533, TOPMed rs773091533, gnomAD rs773091533, REVEL 0.10, CADD 23.90
- A65T (p.Ala65Thr), gnomAD 14-23307960-G-A, REVEL 0.04, CADD 21.50
- A65A (p.Ala65Ala), rs369139282, gnomAD 14-23307962-G-A, CADD 3.43
- A66S (p.Ala66Ser), 1000Genomes rs544188628, ExAC rs544188628, TOPMed rs544188628, gnomAD rs544188628, REVEL 0.05, CADD 17.90
- A66T (p.Ala66Thr), 1000Genomes rs544188628, ExAC rs544188628, TOPMed rs544188628, gnomAD rs544188628, REVEL 0.03, CADD 22.60
- A66A (p.Ala66Ala), rs1222179165, gnomAD 14-23307965-T-C, CADD 12.30
- Q67R (p.Gln67Arg), gnomAD rs1239121868, REVEL 0.31, CADD 26.30
- Q67* (p.Gln67Ter), gnomAD 14-23307966-C-T, CADD 37.00
- L68L (p.Leu68Leu), rs1280829243, gnomAD 14-23307969-C-T, CADD 11.70
- H69R (p.His69Arg), ExAC rs773936872, TOPMed rs773936872, gnomAD rs773936872, REVEL 0.32, CADD 25.80
- H69H (p.His69His), rs1887352347, gnomAD 14-23307974-T-C, CADD 13.10
- T71A (p.Thr71Ala), TOPMed rs1275988727
- T71T (p.Thr71Thr), rs759081269, gnomAD 14-23307980-C-T, CADD 13.80
- P72T (p.Pro72Thr), cosmic curated COSV99161, Ensembl rs1479423139
- P72A (p.Pro72Ala), gnomAD 14-23307981-C-G, REVEL 0.14, CADD 23.00
- P72P (p.Pro72Pro), gnomAD 14-23307983-A-T, CADD 3.65
- G73D (p.Gly73Asp), TOPMed rs1887353630
- S74L (p.Ser74Leu), cosmic curated COSV51635, TOPMed rs1392749158, gnomAD rs1392749158, REVEL 0.14, CADD 24.70
- A75A (p.Ala75Ala), gnomAD 14-23307992-C-T, CADD 10.10
- Q76R (p.Gln76Arg), Ensembl rs1887354090, REVEL 0.10, CADD 18.80
- Q76P (p.Gln76Pro), gnomAD 14-23307994-A-C, REVEL 0.15, CADD 22.90
- Q76Q (p.Gln76Gln), rs1049463, gnomAD 14-23307995-A-G, CADD 9.98
- Q77E (p.Gln77Glu), ExAC rs767286687, gnomAD rs767286687, REVEL 0.05, CADD 22.60
- Q77Q (p.Gln77Gln), rs1789483990, gnomAD 14-23307998-A-G, CADD 7.20
- R78C (p.Arg78Cys), 1000Genomes rs143454020, ESP rs143454020, ExAC rs143454020, TOPMed rs143454020, REVEL 0.10, CADD 26.60
- R78G (p.Arg78Gly), 1000Genomes rs143454020, ESP rs143454020, ExAC rs143454020, TOPMed rs143454020, REVEL 0.10, CADD 23.30
Public BCL2L2 analysis runs
- BCL2L2 analysis run — BCL2L2 (553 variants) — completed 2026-08-20