BCL6 (B-cell lymphoma 6 protein) variants and mutations
BCL6 (also known as B-cell lymphoma 6 protein) is a human protein-coding gene encoding a b-cell lymphoma 6 protein. It temporarily suppresses DNA-damage checkpoints, inflammatory genes, and differentiation programs so germinal-center B cells can proliferate and diversify antibodies. Persistent expression through rearrangement or mutation can drive diffuse large B-cell lymphoma and other lymphoid malignancies. This analysis covers 1,197 BCL6 variants and mutations. Of these, 63% have computational variant effect predictions. Disease context includes diffuse large B-cell lymphoma, neurodegenerative disease, and lymphoid neoplasm. Example BCL6 variants include M1?, A2G, and A2T.
Variant analysis overview
- Gene: BCL6
- Protein: B-cell lymphoma 6 protein
- UniProt accession: P41182
- Organism: Homo sapiens
- Variants analyzed: 1197
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 973 unspecified-consequence records; 127 synonymous variants; 86 missense variants; 1 stop-gained variants; 4 splice-region variants; 1 frameshift variants; 1 in-frame insertions; 1 in-frame deletions; 3 substitution
- Prediction scores: 754 variants have prediction scores (63% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: diffuse large B-cell lymphoma, neurodegenerative disease, lymphoid neoplasm, lymphoma, lung carcinoma, plasma cell myeloma, colorectal adenocarcinoma, skin squamous cell carcinoma, ovarian endometrioid adenocarcinoma with squamous differentiation, myeloproliferative neoplasm, unclassifiable, hemangioblastoma, endometrial endometrioid adenocarcinoma.
Protein structure and variant hotspots
- Protein features: 1 domains; 5 post-translational modification sites.
- Structural context: 63 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, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable BCL6 variants
Examples include M1?, A2G, A2T, A2V, S3A, S3L, P4L, P4S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV51654
- A2G (p.Ala2Gly), gnomAD rs1455072478, REVEL 0.18, CADD 25.10
- A2T (p.Ala2Thr), 1000Genomes rs200997613, ESP rs200997613, TOPMed rs200997613, gnomAD rs200997613, REVEL 0.09, CADD 25.60
- A2V (p.Ala2Val), cosmic curated COSV10802
- S3A (p.Ser3Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S3L (p.Ser3Leu), cosmic curated COSV51655, ESP rs145456310, ExAC rs145456310, TOPMed rs145456310, REVEL 0.05, CADD 23.20
- P4L (p.Pro4Leu), cosmic curated COSV51652, ExAC rs768405263, TOPMed rs768405263, gnomAD rs768405263, REVEL 0.07, CADD 22.40, Uncertain significance, not specified
- P4S (p.Pro4Ser), Ensembl rs2108471787
- A5T (p.Ala5Thr), cosmic curated COSV51653, Ensembl rs2108471773, REVEL 0.09, CADD 22.60
- S7N (p.Ser7Asn), Ensembl rs2108471767
- C8S (p.Cys8Ser), Ensembl rs1719151122
- I9L (p.Ile9Leu), ExAC rs776004818
- Q10* (p.Gln10Ter), gnomAD rs1403542460, CADD 38.00
- Q10R (p.Gln10Arg), cosmic curated COSV51650
- F11S (p.Phe11Ser), gnomAD rs1204164230
- T12I (p.Thr12Ile), Ensembl rs2108471713, REVEL 0.61, CADD 27.30
- T12P (p.Thr12Pro), cosmic curated COSV51652, ExAC rs772289458, gnomAD rs772289458, REVEL 0.61, CADD 28.10
- T12S (p.Thr12Ser), ExAC rs772289458, gnomAD rs772289458
- R13C (p.Arg13Cys), Ensembl rs2108471698
- R13G (p.Arg13Gly), NCI-TCGA Cosmic COSV5165, cosmic curated COSV51652, Variant assessed as somatic; moderate impact.
- R13H (p.Arg13His), cosmic curated COSV51651, Ensembl rs2108471694, REVEL 0.56, CADD 28.60
- H14L (p.His14Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H14R (p.His14Arg), cosmic curated COSV51652
- H14Y (p.His14Tyr), cosmic curated COSV51655
- A15T (p.Ala15Thr), cosmic curated COSV51650
- A15V (p.Ala15Val), Ensembl rs2108471687
- D17E (p.Asp17Glu), Ensembl rs2108471677
- D17V (p.Asp17Val), cosmic curated COSV51650
- L19F (p.Leu19Phe), cosmic curated COSV51654
- L20F (p.Leu20Phe), Ensembl rs2108471669
- N21K (p.Asn21Lys), NCI-TCGA Cosmic COSV5165, cosmic curated COSV51656, REVEL 0.40, CADD 24.00, Variant assessed as somatic; moderate impact.
- L22F (p.Leu22Phe), Ensembl rs2108471663
- N23I (p.Asn23Ile), Ensembl rs2108471658
- R24C (p.Arg24Cys), ExAC rs746411980, gnomAD rs746411980, REVEL 0.62, CADD 32.00
- R24G (p.Arg24Gly), cosmic curated COSV10585
- R24H (p.Arg24His), Ensembl rs752260228, REVEL 0.35, CADD 28.20
- R24S (p.Arg24Ser), NCI-TCGA Cosmic COSV9921, cosmic curated COSV99215, Variant assessed as somatic; moderate impact.
- R26G (p.Arg26Gly), ExAC rs779268890, TOPMed rs779268890, gnomAD rs779268890, Uncertain significance
- R26Q (p.Arg26Gln), cosmic curated COSV10875, REVEL 0.80, CADD 29.40
- R26W (p.Arg26Trp), rs779268890, ClinGen CA2750934, cosmic curated COSV51655, ClinVar RCV004093010, REVEL 0.85, CADD 30.00, Uncertain significance, not specified
- R28* (p.Arg28Ter), cosmic curated COSV51652, ExAC rs11545363, gnomAD rs11545363, REVEL 0.32, CADD 37.00
- R28G (p.Arg28Gly), ExAC rs11545363, gnomAD rs11545363, REVEL 0.63, CADD 27.90
- R28Q (p.Arg28Gln), NCI-TCGA Cosmic COSV1043, cosmic curated COSV10437, REVEL 0.46, CADD 27.60, Variant assessed as somatic; moderate impact.
- D29G (p.Asp29Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D29N (p.Asp29Asn), TOPMed rs1719148297
- I30T (p.Ile30Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V34A (p.Val34Ala), cosmic curated COSV10940, REVEL 0.82, CADD 25.10
- V35A (p.Val35Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V35F (p.Val35Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V37A (p.Val37Ala), Ensembl rs1719147796
- S39N (p.Ser39Asn), ExAC rs778027285, gnomAD rs778027285, REVEL 0.13, CADD 18.90
- S39R (p.Ser39Arg), cosmic curated COSV51652
- R40C (p.Arg40Cys), cosmic curated COSV51650, ESP rs147478441, ExAC rs147478441, TOPMed rs147478441, REVEL 0.46, CADD 29.70
- R40G (p.Arg40Gly), ESP rs147478441, ExAC rs147478441, TOPMed rs147478441, gnomAD rs147478441, REVEL 0.17, CADD 23.60
- R40H (p.Arg40His), 1000Genomes rs573866973, ExAC rs573866973, TOPMed rs573866973, gnomAD rs573866973, REVEL 0.30, CADD 24.00
- R40L (p.Arg40Leu), 1000Genomes rs573866973, ExAC rs573866973, TOPMed rs573866973, gnomAD rs573866973, REVEL 0.41, CADD 23.80
- R40P (p.Arg40Pro), 1000Genomes rs573866973, ExAC rs573866973, TOPMed rs573866973, gnomAD rs573866973
- E41K (p.Glu41Lys), cosmic curated COSV10585
- Q42H (p.Gln42His), TOPMed rs1413816021, gnomAD rs1413816021, REVEL 0.16, CADD 19.80
- A45S (p.Ala45Ser), cosmic curated COSV51656
- H46Y (p.His46Tyr), cosmic curated COSV51651
- K47T (p.Lys47Thr), Ensembl rs2108471555, REVEL 0.91, CADD 27.40
- T48A (p.Thr48Ala), TOPMed rs1719146292, REVEL 0.33, CADD 23.70
- T48M (p.Thr48Met), rs200263685, ClinGen CA157267, cosmic curated COSV51655, ClinVar RCV000120197, REVEL 0.44, CADD 28.90, not provided, not specified
- V49I (p.Val49Ile), cosmic curated COSV51650, REVEL 0.32, CADD 23.40
- L50F (p.Leu50Phe), cosmic curated COSV10634
- L50H (p.Leu50His), Ensembl rs2108471523
- M51V (p.Met51Val), cosmic curated COSV10508
- A52G (p.Ala52Gly), Ensembl rs2108471511
- G55D (p.Gly55Asp), cosmic curated COSV51654
- F57L (p.Phe57Leu), gnomAD rs1415288002, NCI-TCGA Cosmic COSV9921, cosmic curated COSV99215, REVEL 0.80, CADD 26.30, Variant assessed as somatic; moderate impact.
- Y58C (p.Tyr58Cys), cosmic curated COSV51653
- S59G (p.Ser59Gly), ExAC rs752436963, gnomAD rs752436963, REVEL 0.35, CADD 27.00
- S59N (p.Ser59Asn), cosmic curated COSV10608, TOPMed rs1474668374, gnomAD rs1474668374, REVEL 0.23, CADD 26.80
- I60T (p.Ile60Thr), Ensembl rs955595035
- I60V (p.Ile60Val), gnomAD rs1260913176
- F61L (p.Phe61Leu), TOPMed rs1327801709, gnomAD rs1327801709, REVEL 0.72, CADD 24.70
- F61Y (p.Phe61Tyr), cosmic curated COSV10875
- T62I (p.Thr62Ile), TOPMed rs1719065575, REVEL 0.59, CADD 27.20
- D63E (p.Asp63Glu), Ensembl rs1719065143
- N68I (p.Asn68Ile), cosmic curated COSV99215
- N68K (p.Asn68Lys), ExAC rs767073067, gnomAD rs767073067, REVEL 0.31, CADD 25.40
- N68S (p.Asn68Ser), cosmic curated COSV51652, TOPMed rs911170380, gnomAD rs911170380, REVEL 0.27, CADD 24.30
- L69P (p.Leu69Pro), cosmic curated COSV51653
- S70N (p.Ser70Asn), cosmic curated COSV51654
- N73D (p.Asn73Asp), TOPMed rs1202329522, gnomAD rs1202329522, REVEL 0.37, CADD 27.10
- N73S (p.Asn73Ser), rs760006045, NCI-TCGA Cosmic COSV5165, cosmic curated COSV51650, ExAC rs760006045, REVEL 0.17, CADD 23.00, Variant assessed as somatic; moderate impact.
- L74I (p.Leu74Ile), Ensembl rs1719063001
- D75Y (p.Asp75Tyr), Ensembl rs1579816551
- P76S (p.Pro76Ser), cosmic curated COSV51653
- E77D (p.Glu77Asp), gnomAD rs1275125976, REVEL 0.09, CADD 19.10
- I78M (p.Ile78Met), rs774593110, ClinGen CA2750900, ClinVar RCV004140630, ExAC rs774593110, REVEL 0.33, CADD 25.40, Uncertain significance, not specified
- I78V (p.Ile78Val), cosmic curated COSV10585
- N79S (p.Asn79Ser), ExAC rs771261860, REVEL 0.10, CADD 21.30
- P80S (p.Pro80Ser), ExAC rs763472780, gnomAD rs763472780, REVEL 0.44, CADD 23.70
- G82* (p.Gly82Ter), cosmic curated COSV10605
- G82E (p.Gly82Glu), Ensembl rs1719061731
- C84S (p.Cys84Ser), TOPMed rs1225779160, gnomAD rs1225779160, REVEL 0.18, CADD 20.80
- I85V (p.Ile85Val), ExAC rs769899811, gnomAD rs769899811, REVEL 0.08, CADD 19.90
- F89L (p.Phe89Leu), ESP rs148348997, TOPMed rs148348997, gnomAD rs148348997, REVEL 0.80, CADD 24.00
- M90I (p.Met90Ile), cosmic curated COSV51653
- M90L (p.Met90Leu), cosmic curated COSV51654
- T92I (p.Thr92Ile), NCI-TCGA Cosmic COSV5165, cosmic curated COSV51655, Variant assessed as somatic; moderate impact.
- R94Q (p.Arg94Gln), rs768771889, NCI-TCGA Cosmic COSV9921, cosmic curated COSV99215, ExAC rs768771889, REVEL 0.34, CADD 24.90, Uncertain significance, not specified
- R94W (p.Arg94Trp), rs781532443, NCI-TCGA Cosmic COSV5165, cosmic curated COSV51656, ExAC rs781532443, REVEL 0.70, CADD 26.30, Variant assessed as somatic; moderate impact.
- R98P (p.Arg98Pro), TOPMed rs1391779185, gnomAD rs1391779185, REVEL 0.46, CADD 27.60
- R98Q (p.Arg98Gln), cosmic curated COSV10634, TOPMed rs1391779185, gnomAD rs1391779185, REVEL 0.24, CADD 26.70
- R98W (p.Arg98Trp), cosmic curated COSV10634, TOPMed rs867240773, gnomAD rs867240773, REVEL 0.54, CADD 27.40
- E99K (p.Glu99Lys), cosmic curated COSV10457
- G100D (p.Gly100Asp), ESP rs377166099, ExAC rs377166099, gnomAD rs377166099, REVEL 0.19, CADD 21.90
- G100S (p.Gly100Ser), ExAC rs757071785, TOPMed rs757071785, gnomAD rs757071785, REVEL 0.07, CADD 16.80
- G100V (p.Gly100Val), ESP rs377166099, ExAC rs377166099, gnomAD rs377166099
- M103I (p.Met103Ile), ExAC rs777825559, TOPMed rs777825559, gnomAD rs777825559, REVEL 0.36, CADD 23.70
- M103V (p.Met103Val), Ensembl rs1719058118
- A104V (p.Ala104Val), NCI-TCGA Cosmic COSV5165, cosmic curated COSV51651, Variant assessed as somatic; moderate impact.
- V105G (p.Val105Gly), Ensembl rs200844445
- V105M (p.Val105Met), cosmic curated COSV51653
- M106V (p.Met106Val), Ensembl rs201271781
- A107T (p.Ala107Thr), rs752135848, ClinGen CA2750886, ClinVar RCV004255644, ExAC rs752135848, REVEL 0.09, CADD 18.80, Uncertain significance, not specified
- T108A (p.Thr108Ala), Ensembl rs1026114025, REVEL 0.33, CADD 23.70
- T108M (p.Thr108Met), Ensembl rs1719056630, REVEL 0.66, CADD 29.20
- M110I (p.Met110Ile), gnomAD rs1719056080, REVEL 0.17, CADD 17.20
- M110V (p.Met110Val), TOPMed rs1719056277, REVEL 0.16, CADD 20.20
- L112P (p.Leu112Pro), NCI-TCGA Cosmic COSV5165, cosmic curated COSV51651, Variant assessed as somatic; moderate impact.
- Q113H (p.Gln113His), TOPMed rs1719055545, REVEL 0.76, CADD 24.60
- Q113K (p.Gln113Lys), ExAC rs754593601, gnomAD rs754593601, REVEL 0.63, CADD 24.90
- M114I (p.Met114Ile), cosmic curated COSV51651
- E115Q (p.Glu115Gln), TOPMed rs1719055352
- H116R (p.His116Arg), gnomAD rs1218169171, REVEL 0.64, CADD 26.60
- V117F (p.Val117Phe), rs866452181, NCI-TCGA Cosmic COSV5165, cosmic curated COSV51651, Ensembl rs866452181, AlphaMissense 0.97, MetaLR 0.72, Variant assessed as somatic; moderate impact.
- D119N (p.Asp119Asn), ExAC rs751185760, gnomAD rs751185760, REVEL 0.46, CADD 25.20
- T120S (p.Thr120Ser), TOPMed rs1719053867, gnomAD rs1719053867, REVEL 0.33, CADD 26.40
- C121S (p.Cys121Ser), cosmic curated COSV51652
- R122Q (p.Arg122Gln), rs372779365, cosmic curated COSV51651, 1000Genomes rs372779365, ESP rs372779365, REVEL 0.10, CADD 23.70, Variant assessed as somatic; moderate impact.
- R122W (p.Arg122Trp), cosmic curated COSV51651, 1000Genomes rs551620719, ExAC rs551620719, TOPMed rs551620719, REVEL 0.43, CADD 32.00
- K123* (p.Lys123Ter), cosmic curated COSV51653
- K123E (p.Lys123Glu), Ensembl rs1579816227
- K123R (p.Lys123Arg), ExAC rs773775457, gnomAD rs773775457, REVEL 0.11, CADD 20.60
- F124V (p.Phe124Val), Ensembl rs1579816201
- I125F (p.Ile125Phe), gnomAD rs1719052274, REVEL 0.38, CADD 24.00
- K126N (p.Lys126Asn), gnomAD rs1719051924, REVEL 0.23, CADD 17.70
- K126R (p.Lys126Arg), ExAC rs765718723
- A127P (p.Ala127Pro), gnomAD rs1368125173
- A127S (p.Ala127Ser), cosmic curated COSV99215
- S128R (p.Ser128Arg), Ensembl rs1309836914
- E129* (p.Glu129Ter), gnomAD rs1261239948, CADD 41.00
- A130G (p.Ala130Gly), Ensembl rs1718960740
- A130T (p.Ala130Thr), ExAC rs748058804, gnomAD rs748058804, REVEL 0.12, CADD 20.80
- E131D (p.Glu131Asp), 1000Genomes rs376615026, ESP rs376615026, ExAC rs376615026, TOPMed rs376615026, REVEL 0.15, CADD 21.10, Uncertain significance, not specified
- M132V (p.Met132Val), TOPMed rs1718960312
- V133I (p.Val133Ile), gnomAD rs1258651142, REVEL 0.03, CADD 15.90
- S134F (p.Ser134Phe), Ensembl rs922510534, REVEL 0.11, CADD 23.00
- S134P (p.Ser134Pro), gnomAD rs1210690719, REVEL 0.01, CADD 19.70
- A135S (p.Ala135Ser), Ensembl rs1236418654
- I136V (p.Ile136Val), gnomAD rs1484945872, REVEL 0.02, CADD 10.80
- K137N (p.Lys137Asn), TOPMed rs1718958703, REVEL 0.11, CADD 20.90
- K137R (p.Lys137Arg), TOPMed rs1718958956
- P138A (p.Pro138Ala), ExAC rs746514494, gnomAD rs746514494, REVEL 0.06, CADD 15.70
- P138L (p.Pro138Leu), 1000Genomes rs555800838, ExAC rs555800838, TOPMed rs555800838, gnomAD rs555800838, REVEL 0.07, CADD 17.50
- P138R (p.Pro138Arg), 1000Genomes rs555800838, ExAC rs555800838, TOPMed rs555800838, gnomAD rs555800838, REVEL 0.11, CADD 19.00
- P138S (p.Pro138Ser), ExAC rs746514494, gnomAD rs746514494, REVEL 0.04, CADD 18.00
- P138T (p.Pro138Thr), ExAC rs746514494, gnomAD rs746514494
- P139L (p.Pro139Leu), ExAC rs750032802, gnomAD rs750032802, REVEL 0.21, CADD 18.90
- P139S (p.Pro139Ser), cosmic curated COSV51654, ExAC rs758046316, TOPMed rs758046316, gnomAD rs758046316, REVEL 0.03, CADD 16.10
- R140C (p.Arg140Cys), rs779270221, NCI-TCGA Cosmic COSV5165, cosmic curated COSV51655, ExAC rs779270221, REVEL 0.16, CADD 24.70, Variant assessed as somatic; moderate impact.
- R140H (p.Arg140His), rs536118071, NCI-TCGA Cosmic COSV5165, cosmic curated COSV51650, 1000Genomes rs536118071, REVEL 0.14, CADD 22.40, Variant assessed as somatic; moderate impact.
- R140L (p.Arg140Leu), 1000Genomes rs536118071, ExAC rs536118071, TOPMed rs536118071, gnomAD rs536118071, REVEL 0.26, CADD 22.50
- E141K (p.Glu141Lys), cosmic curated COSV51654
- E142A (p.Glu142Ala), TOPMed rs777622359, gnomAD rs777622359, REVEL 0.12, CADD 23.70
- E142D (p.Glu142Asp), cosmic curated COSV51652
- E142Q (p.Glu142Gln), cosmic curated COSV51652, REVEL 0.12, CADD 23.10
- L144F (p.Leu144Phe), gnomAD rs1398495055, REVEL 0.07, CADD 22.60
- L144H (p.Leu144His), 1000Genomes rs144416315, ESP rs144416315, ExAC rs144416315, TOPMed rs144416315, REVEL 0.18, CADD 24.30
- N145H (p.Asn145His), rs944713285, ClinGen CA89693209, ClinVar RCV004296042, TOPMed rs944713285, REVEL 0.05, CADD 17.90, Uncertain significance, not specified
- R147L (p.Arg147Leu), cosmic curated COSV99215
- R147P (p.Arg147Pro), cosmic curated COSV51655, ExAC rs760727857, TOPMed rs760727857, gnomAD rs760727857, REVEL 0.15, CADD 24.20
- R147Q (p.Arg147Gln), ExAC rs760727857, TOPMed rs760727857, gnomAD rs760727857, REVEL 0.14, CADD 24.00
- R147W (p.Arg147Trp), rs754091486, ClinGen CA89693206, cosmic curated COSV51650, ClinVar RCV004294914, REVEL 0.24, CADD 29.90, Uncertain significance, not specified
- M148T (p.Met148Thr), 1000Genomes rs201608619, ExAC rs201608619, gnomAD rs201608619, REVEL 0.17, CADD 21.60
- M150R (p.Met150Arg), TOPMed rs1279740465, gnomAD rs1279740465, REVEL 0.18, CADD 22.20
Public BCL6 analysis runs
- BCL6 analysis run — BCL6 (1,197 variants) — completed 2026-08-18