MCL1 (Q07820) variants and mutations
MCL1 (also known as Q07820) is a human protein-coding gene encoding an induced myeloid leukemia cell differentiation protein Mcl-1 protein. It provides a rapidly regulated anti-apoptotic signal at mitochondria by sequestering pro-death BCL-2-family proteins. Many cancers become dependent on elevated MCL1 for survival, making it an important target for anticancer drug development. This analysis covers 1,129 MCL1 variants and mutations. Of these, 64% have computational variant effect predictions. Disease context includes neurodegenerative disease, Abnormality of the skeletal system, and prostate carcinoma. Example MCL1 variants include F2L, G3D, and L4F.
Variant analysis overview
- Gene: MCL1
- Protein: Q07820
- UniProt accession: Q07820
- Organism: Homo sapiens
- Variants analyzed: 1129
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 898 unspecified-consequence records; 1 stop lost; 99 missense variants; 6 frameshift variants; 110 synonymous variants; 6 in-frame deletions; 2 stop-gained variants; 2 splice-region variants; 3 in-frame insertions; 2 substitution
- Prediction scores: 718 variants have prediction scores (64% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, Abnormality of the skeletal system, prostate carcinoma, Epidermal Inclusion Cyst, small cell lung carcinoma, coronary artery disorder, cancer, myocardial ischemia, colorectal carcinoma, Oral ulcer, ovarian carcinoma, acute myeloid leukemia.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 4 post-translational modification sites.
- Structural context: 54 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 MCL1 variants
Examples include F2L, G3D, L4F, L4H, L4P, L4V, R6K, N7K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- F2L (p.Phe2Leu), gnomAD rs1465779538, REVEL 0.04, CADD 19.90
- G3D (p.Gly3Asp), TOPMed rs1647992648, REVEL 0.11, CADD 22.50
- L4F (p.Leu4Phe), cosmic curated COSV57190, gnomAD rs1647992246, REVEL 0.02, CADD 13.10
- L4H (p.Leu4His), gnomAD rs1206343665, REVEL 0.15, CADD 24.20
- L4P (p.Leu4Pro), gnomAD rs1206343665, REVEL 0.23, CADD 23.30
- L4V (p.Leu4Val), gnomAD rs1647992246
- R6K (p.Arg6Lys), Ensembl rs2101701072, REVEL 0.06, CADD 17.10
- N7K (p.Asn7Lys), TOPMed rs1647991739, gnomAD rs1647991739, REVEL 0.14, CADD 23.80
- A8E (p.Ala8Glu), gnomAD rs1445925900, REVEL 0.18, CADD 27.50
- A8G (p.Ala8Gly), gnomAD rs1445925900, REVEL 0.09, CADD 24.40
- A8V (p.Ala8Val), cosmic curated COSV57191, gnomAD rs1445925900, REVEL 0.13, CADD 24.20
- V9E (p.Val9Glu), gnomAD rs1647991394, REVEL 0.28, CADD 26.40
- V9I (p.Val9Ile), Ensembl rs2101701050
- I10F (p.Ile10Phe), Ensembl rs2101701040
- I10N (p.Ile10Asn), Ensembl rs2101701034
- G11R (p.Gly11Arg), TOPMed rs1647991185
- L12F (p.Leu12Phe), gnomAD rs1229708032, REVEL 0.12, CADD 23.90
- L12V (p.Leu12Val), gnomAD rs1229708032, REVEL 0.14, CADD 23.40
- N13I (p.Asn13Ile), Ensembl rs2101701000
- N13K (p.Asn13Lys), ExAC rs779751278, TOPMed rs779751278, gnomAD rs779751278, REVEL 0.12, CADD 24.40
- L14F (p.Leu14Phe), 1000Genomes rs587612386, ExAC rs587612386, TOPMed rs587612386, gnomAD rs587612386, REVEL 0.08, CADD 24.10
- L14P (p.Leu14Pro), Ensembl rs2101700983
- L14V (p.Leu14Val), 1000Genomes rs587612386, ExAC rs587612386, TOPMed rs587612386, gnomAD rs587612386, REVEL 0.09, CADD 23.80
- Y15F (p.Tyr15Phe), Ensembl rs2101700976
- C16S (p.Cys16Ser), Ensembl rs2101700960
- C16W (p.Cys16Trp), ExAC rs756447542, gnomAD rs756447542
- C16Y (p.Cys16Tyr), Ensembl rs2101700960, REVEL 0.22, CADD 23.20
- G17A (p.Gly17Ala), TOPMed rs1012747207, gnomAD rs1012747207, REVEL 0.12, CADD 23.20
- G17E (p.Gly17Glu), cosmic curated COSV57190, TOPMed rs1012747207, gnomAD rs1012747207, REVEL 0.23, CADD 25.20
- G17R (p.Gly17Arg), TOPMed rs932863734, gnomAD rs932863734, REVEL 0.23, CADD 26.70
- G17V (p.Gly17Val), TOPMed rs1012747207, gnomAD rs1012747207, REVEL 0.19, CADD 23.20
- G17W (p.Gly17Trp), TOPMed rs932863734, gnomAD rs932863734, REVEL 0.25, CADD 28.30
- G18W (p.Gly18Trp), ExAC rs753196937, gnomAD rs753196937, REVEL 0.24, CADD 26.10
- A19G (p.Ala19Gly), cosmic curated COSV57189, TOPMed rs1490867890, REVEL 0.04, CADD 22.50
- A19P (p.Ala19Pro), TOPMed rs1249841412, gnomAD rs1249841412, REVEL 0.09, CADD 20.60
- A19V (p.Ala19Val), rs1490867890, NCI-TCGA Cosmic COSV5718, cosmic curated COSV57189, REVEL 0.09, CADD 23.40, Variant assessed as somatic; moderate impact.
- G20D (p.Gly20Asp), Ensembl rs1647988095, REVEL 0.13, CADD 22.90
- G20S (p.Gly20Ser), Ensembl rs1570984132, REVEL 0.02, CADD 17.70
- L21F (p.Leu21Phe), ExAC rs751612946, TOPMed rs751612946, gnomAD rs751612946, REVEL 0.07, CADD 16.50
- L21M (p.Leu21Met), ExAC rs755515463, gnomAD rs755515463
- L21V (p.Leu21Val), ExAC rs755515463, gnomAD rs755515463, REVEL 0.02, CADD 6.03
- G22A (p.Gly22Ala), ExAC rs766507232, gnomAD rs766507232, REVEL 0.07, CADD 8.51
- G22E (p.Gly22Glu), ExAC rs766507232, gnomAD rs766507232, REVEL 0.12, CADD 15.70
- A23T (p.Ala23Thr), Ensembl rs1560317102, REVEL 0.02, CADD 17.60
- A23V (p.Ala23Val), ExAC rs750616819, gnomAD rs750616819, REVEL 0.04, CADD 20.20
- G24D (p.Gly24Asp), Ensembl rs2101700813, REVEL 0.15, CADD 22.90
- G24S (p.Gly24Ser), ExAC rs761537521, gnomAD rs761537521, REVEL 0.05, CADD 16.60
- S25G (p.Ser25Gly), TOPMed rs1647986714, gnomAD rs1647986714, REVEL 0.02, CADD 7.15
- S25I (p.Ser25Ile), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10032, Variant assessed as somatic; moderate impact.
- S25N (p.Ser25Asn), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10032, Ensembl rs2101700789, Variant assessed as somatic; moderate impact.
- S25R (p.Ser25Arg), Ensembl rs1378207194, REVEL 0.07, CADD 18.60
- G26S (p.Gly26Ser), gnomAD rs925013521, REVEL 0.02, CADD 16.30
- G27D (p.Gly27Asp), TOPMed rs936472592, REVEL 0.10, CADD 23.20
- A28G (p.Ala28Gly), Ensembl rs2101700741
- A28P (p.Ala28Pro), ExAC rs768684341, TOPMed rs768684341, gnomAD rs768684341, REVEL 0.16, CADD 22.70
- A28S (p.Ala28Ser), ExAC rs768684341, TOPMed rs768684341, gnomAD rs768684341
- A28T (p.Ala28Thr), ExAC rs768684341, TOPMed rs768684341, gnomAD rs768684341, REVEL 0.04, CADD 19.90, Uncertain significance, not specified
- A28V (p.Ala28Val), Ensembl rs2101700741, REVEL 0.05, CADD 19.20
- T29I (p.Thr29Ile), 1000Genomes rs775135247, ExAC rs775135247, gnomAD rs775135247, REVEL 0.04, CADD 22.10
- T29S (p.Thr29Ser), cosmic curated COSV57190, 1000Genomes rs775135247, ExAC rs775135247, gnomAD rs775135247, REVEL 0.06, CADD 13.30
- R30C (p.Arg30Cys), ExAC rs771486484, gnomAD rs771486484, REVEL 0.01, CADD 16.00
- R30G (p.Arg30Gly), ExAC rs771486484, gnomAD rs771486484
- R30H (p.Arg30His), TOPMed rs1024728611, gnomAD rs1024728611, REVEL 0.12, CADD 21.90
- R30P (p.Arg30Pro), TOPMed rs1024728611, gnomAD rs1024728611
- P31A (p.Pro31Ala), TOPMed rs1188100637, gnomAD rs1188100637, REVEL 0.04, CADD 5.66
- P31L (p.Pro31Leu), ExAC rs745465126, TOPMed rs745465126, gnomAD rs745465126, REVEL 0.06, CADD 22.40
- P31R (p.Pro31Arg), ExAC rs745465126, TOPMed rs745465126, gnomAD rs745465126, REVEL 0.03, CADD 18.10
- P31S (p.Pro31Ser), cosmic curated COSV57189, TOPMed rs1188100637, gnomAD rs1188100637
- G32A (p.Gly32Ala), ExAC rs770152297, TOPMed rs770152297, gnomAD rs770152297, REVEL 0.03, CADD 9.05, Uncertain significance, not specified
- G32E (p.Gly32Glu), cosmic curated COSV57190, ExAC rs770152297, TOPMed rs770152297, gnomAD rs770152297, REVEL 0.04, CADD 16.60
- G32R (p.Gly32Arg), cosmic curated COSV10647, TOPMed rs1647984686, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G33A (p.Gly33Ala), TOPMed rs902324572, gnomAD rs902324572, REVEL 0.04, CADD 9.70
- G33E (p.Gly33Glu), TOPMed rs902324572, gnomAD rs902324572, REVEL 0.01, CADD 13.60
- G33R (p.Gly33Arg), TOPMed rs1647984298
- G33W (p.Gly33Trp), TOPMed rs1647984298, REVEL 0.04, CADD 20.30
- R34* (p.Arg34Ter), ExAC rs748428410, gnomAD rs748428410, CADD 34.00
- R34G (p.Arg34Gly), ExAC rs748428410, gnomAD rs748428410, REVEL 0.05, CADD 15.50
- R34L (p.Arg34Leu), Ensembl rs2101700616
- R34P (p.Arg34Pro), Ensembl rs2101700616
- R34Q (p.Arg34Gln), Ensembl rs2101700616, REVEL 0.02, CADD 14.50
- L35P (p.Leu35Pro), Ensembl rs1013421918
- L35V (p.Leu35Val), Ensembl rs2101700602
- L36F (p.Leu36Phe), TOPMed rs1647983559
- L36S (p.Leu36Ser), Ensembl rs1570984004, REVEL 0.07, CADD 12.60
- A37G (p.Ala37Gly), Ensembl rs2101700584
- A37V (p.Ala37Val), Ensembl rs2101700584
- A37A (p.Ala37Ala), rs199699332, gnomAD 1-150578961-G-A, CADD 6.60
- T38K (p.Thr38Lys), TOPMed rs1168893169, gnomAD rs1168893169, REVEL 0.04, CADD 10.60
- T38M (p.Thr38Met), TOPMed rs1168893169, gnomAD rs1168893169, REVEL 0.06, CADD 14.20
- T38R (p.Thr38Arg), TOPMed rs1168893169, gnomAD rs1168893169
- T38S (p.Thr38Ser), 1000Genomes rs768191690, ExAC rs768191690, TOPMed rs768191690, gnomAD rs768191690, REVEL 0.01, CADD 0.04, Uncertain significance, not specified
- E39G (p.Glu39Gly), gnomAD rs1428492838, REVEL 0.09, CADD 16.90
- K40E (p.Lys40Glu), ExAC rs755460962, gnomAD rs755460962, REVEL 0.14, CADD 22.20
- K40Q (p.Lys40Gln), ExAC rs755460962, gnomAD rs755460962
- E41G (p.Glu41Gly), TOPMed rs985143129, REVEL 0.06, CADD 22.90
- E41K (p.Glu41Lys), TOPMed rs898520253, gnomAD rs898520253, REVEL 0.09, CADD 22.90
- A42G (p.Ala42Gly), ExAC rs780046930, TOPMed rs780046930, gnomAD rs780046930
- A42P (p.Ala42Pro), ExAC rs373644818, TOPMed rs373644818, gnomAD rs373644818, REVEL 0.05, CADD 22.30
- A42S (p.Ala42Ser), ExAC rs373644818, TOPMed rs373644818, gnomAD rs373644818
- A42T (p.Ala42Thr), ExAC rs373644818, TOPMed rs373644818, gnomAD rs373644818
- A42V (p.Ala42Val), ExAC rs780046930, TOPMed rs780046930, gnomAD rs780046930, REVEL 0.11, CADD 23.20, Uncertain significance, not specified
- S43L (p.Ser43Leu), gnomAD rs1267652025, REVEL 0.02, CADD 16.50
- S43P (p.Ser43Pro), Ensembl rs2101700481, REVEL 0.01, CADD 5.45
- S43T (p.Ser43Thr), Ensembl rs2101700481
- S43W (p.Ser43Trp), cosmic curated COSV57189, gnomAD rs1267652025, REVEL 0.04, CADD 21.90
- A44S (p.Ala44Ser), ExAC rs758423754, TOPMed rs758423754, gnomAD rs758423754, REVEL 0.03, CADD 13.20
- A44T (p.Ala44Thr), ExAC rs758423754, TOPMed rs758423754, gnomAD rs758423754, REVEL 0.06, CADD 14.80
- A44V (p.Ala44Val), rs919674275, ClinGen CA30087836, cosmic curated COSV57191, ClinVar RCV004318811, REVEL 0.09, CADD 20.60, Uncertain significance, not specified
- R45L (p.Arg45Leu), Ensembl rs1004335558
- R45P (p.Arg45Pro), Ensembl rs1004335558
- R45Q (p.Arg45Gln), Ensembl rs1004335558, REVEL 0.07, CADD 13.10
- R45W (p.Arg45Trp), rs587712554, ClinGen CA342326921, cosmic curated COSV57190, ClinVar RCV004098987, REVEL 0.13, CADD 22.30, Uncertain significance, not specified
- R46* (p.Arg46Ter), Ensembl rs2101700433, CADD 34.00
- R46G (p.Arg46Gly), Ensembl rs2101700433
- R46Q (p.Arg46Gln), cosmic curated COSV10588, Ensembl rs61819445, REVEL 0.03, CADD 14.90
- E47D (p.Glu47Asp), cosmic curated COSV57191, Ensembl rs2101700422, REVEL 0.05, CADD 15.10
- I48K (p.Ile48Lys), cosmic curated COSV57190, ExAC rs765410863, TOPMed rs765410863, gnomAD rs765410863
- I48M (p.Ile48Met), TOPMed rs1647980280, gnomAD rs1647980280, REVEL 0.06, CADD 14.90, Uncertain significance, not specified
- I48R (p.Ile48Arg), ExAC rs765410863, TOPMed rs765410863, gnomAD rs765410863, REVEL 0.03, CADD 3.23
- I48V (p.Ile48Val), Ensembl rs891225396, REVEL 0.02, CADD 8.31
- G49A (p.Gly49Ala), ExAC rs757542528, TOPMed rs757542528, gnomAD rs757542528, REVEL 0.16, CADD 23.40
- G49E (p.Gly49Glu), ExAC rs757542528, TOPMed rs757542528, gnomAD rs757542528, REVEL 0.24, CADD 24.00
- G49R (p.Gly49Arg), cosmic curated COSV57190, gnomAD rs1312773225, REVEL 0.20, CADD 25.40
- G49W (p.Gly49Trp), gnomAD rs1312773225, REVEL 0.25, CADD 26.40
- G50R (p.Gly50Arg), Ensembl rs2101700372, REVEL 0.09, CADD 24.00
- G50V (p.Gly50Val), TOPMed rs1647979754, REVEL 0.09, CADD 20.20
- G51A (p.Gly51Ala), ExAC rs753664661, gnomAD rs753664661, REVEL 0.02, CADD 19.10
- G51E (p.Gly51Glu), NCI-TCGA TCGA novel, REVEL 0.10, CADD 22.30, Variant assessed as somatic; moderate impact.
- G51V (p.Gly51Val), ExAC rs753664661, gnomAD rs753664661, REVEL 0.04, CADD 23.10
- G51W (p.Gly51Trp), Ensembl rs2101700355, REVEL 0.12, CADD 27.40
- E52D (p.Glu52Asp), NCI-TCGA TCGA novel, REVEL 0.13, CADD 9.47, Variant assessed as somatic; moderate impact.
- A53G (p.Ala53Gly), Ensembl rs2101700319
- A53P (p.Ala53Pro), ExAC rs764039573, TOPMed rs764039573, gnomAD rs764039573, REVEL 0.15, CADD 21.70
- A53T (p.Ala53Thr), ExAC rs764039573, TOPMed rs764039573, gnomAD rs764039573, REVEL 0.02, CADD 20.40
- A53V (p.Ala53Val), Ensembl rs2101700319, REVEL 0.04, CADD 17.90
- G54C (p.Gly54Cys), ExAC rs760622088, TOPMed rs760622088, gnomAD rs760622088, REVEL 0.17, CADD 24.40
- G54D (p.Gly54Asp), Ensembl rs2101700299
- G54S (p.Gly54Ser), ExAC rs760622088, TOPMed rs760622088, gnomAD rs760622088, REVEL 0.18, CADD 22.50
- A55E (p.Ala55Glu), ExAC rs775581615, TOPMed rs775581615, gnomAD rs775581615, REVEL 0.03, CADD 6.97
- A55G (p.Ala55Gly), ExAC rs775581615, TOPMed rs775581615, gnomAD rs775581615
- A55T (p.Ala55Thr), Ensembl rs2101700296, REVEL 0.02, CADD 9.03
- A55V (p.Ala55Val), ExAC rs775581615, TOPMed rs775581615, gnomAD rs775581615, REVEL 0.03, CADD 8.85
- V56G (p.Val56Gly), gnomAD rs1347620252, REVEL 0.08, CADD 11.00
- V56L (p.Val56Leu), Ensembl rs2101700281, REVEL 0.07, CADD 10.40
- V56M (p.Val56Met), Ensembl rs2101700281, REVEL 0.10, CADD 13.30
- I57M (p.Ile57Met), ExAC rs758996875, TOPMed rs758996875, gnomAD rs758996875, REVEL 0.07, CADD 9.05
- I57S (p.Ile57Ser), 1000Genomes rs587657093, ExAC rs587657093, TOPMed rs587657093, gnomAD rs587657093
- I57T (p.Ile57Thr), 1000Genomes rs587657093, ExAC rs587657093, TOPMed rs587657093, gnomAD rs587657093, REVEL 0.06, CADD 7.65
- G58A (p.Gly58Ala), ExAC rs773949054, TOPMed rs773949054, gnomAD rs773949054
- G58C (p.Gly58Cys), Ensembl rs2101700240, REVEL 0.13, CADD 23.40
- G58V (p.Gly58Val), ExAC rs773949054, TOPMed rs773949054, gnomAD rs773949054, REVEL 0.16, CADD 19.40
- G59E (p.Gly59Glu), cosmic curated COSV57189, gnomAD rs1647977930, REVEL 0.17, CADD 20.00
- G59R (p.Gly59Arg), Ensembl rs2101700229, REVEL 0.16, CADD 20.20
- S60C (p.Ser60Cys), Ensembl rs2101700214, REVEL 0.09, CADD 21.80
- S60G (p.Ser60Gly), Ensembl rs2101700214
- S60R (p.Ser60Arg), Ensembl rs2101700207, REVEL 0.08, CADD 14.60
- A61G (p.Ala61Gly), TOPMed rs1647977721
- A61S (p.Ala61Ser), gnomAD rs1467738642, REVEL 0.05, CADD 6.15
- A61T (p.Ala61Thr), gnomAD rs1467738642, REVEL 0.07, CADD 8.96
- A61V (p.Ala61Val), TOPMed rs1647977721, REVEL 0.09, CADD 10.70
- G62A (p.Gly62Ala), TOPMed rs1381690946, gnomAD rs1381690946
- G62D (p.Gly62Asp), TOPMed rs1381690946, gnomAD rs1381690946, REVEL 0.12, CADD 18.40
- G62S (p.Gly62Ser), TOPMed rs1316883818, gnomAD rs1316883818, REVEL 0.04, CADD 12.80
- A63G (p.Ala63Gly), Ensembl rs2101700171
- A63T (p.Ala63Thr), Ensembl rs2101700177, REVEL 0.09, CADD 17.70
- S64G (p.Ser64Gly), Ensembl rs2101700161, REVEL 0.04, CADD 15.00
- S64I (p.Ser64Ile), ExAC rs770464201, gnomAD rs770464201, REVEL 0.11, CADD 19.50
- S64R (p.Ser64Arg), cosmic curated COSV10647, 1000Genomes rs748994212, ExAC rs748994212, TOPMed rs748994212, REVEL 0.12, CADD 14.40
- S64T (p.Ser64Thr), ExAC rs770464201, gnomAD rs770464201
- P65L (p.Pro65Leu), cosmic curated COSV57190, TOPMed rs1473394310, gnomAD rs1473394310, REVEL 0.09, CADD 22.00
- P65R (p.Pro65Arg), TOPMed rs1473394310, gnomAD rs1473394310, REVEL 0.08, CADD 23.20
- P65S (p.Pro65Ser), TOPMed rs1312196037, gnomAD rs1312196037, REVEL 0.09, CADD 18.00
- P66L (p.Pro66Leu), ExAC rs747459222, TOPMed rs747459222, gnomAD rs747459222, REVEL 0.03, CADD 21.90
- P66Q (p.Pro66Gln), rs747459222, ExAC rs747459222, TOPMed rs747459222, gnomAD rs747459222, REVEL 0.04, CADD 16.80, Variant assessed as somatic; moderate impact.
- P66S (p.Pro66Ser), TOPMed rs1647976538, REVEL 0.04, CADD 19.30
- P66T (p.Pro66Thr), TOPMed rs1647976538, REVEL 0.03, CADD 18.70
- S67A (p.Ser67Ala), TOPMed rs1245371992, gnomAD rs1245371992, REVEL 0.01, CADD 1.43
- S67F (p.Ser67Phe), cosmic curated COSV10588, Ensembl rs1647975969, REVEL 0.07, CADD 17.80
- S67P (p.Ser67Pro), TOPMed rs1245371992, gnomAD rs1245371992, REVEL 0.05, CADD 9.76
- S67T (p.Ser67Thr), TOPMed rs1245371992, gnomAD rs1245371992
Public MCL1 analysis runs
- MCL1 analysis run — MCL1 (1,129 variants) — completed 2026-08-19