MCM5 (P33992) variants and mutations
MCM5 (also known as P33992) is a human protein-coding gene encoding a DNA replication licensing factor protein. It functions within the MCM2-7 helicase complex required for origin licensing and DNA unwinding during replication. Because its expression tracks proliferative activity, altered abundance is frequently observed in cancers and is used as a proliferation-related biomarker. This analysis covers 1,055 MCM5 variants and mutations. Of these, 82% have computational variant effect predictions. Disease context includes Ear-patella-short stature syndrome, neurodegenerative disease, and lysosomal storage disease. Example MCM5 variants include S2L, S2*, and S2S.
Variant analysis overview
- Gene: MCM5
- Protein: P33992
- UniProt accession: P33992
- Organism: Homo sapiens
- Variants analyzed: 1055
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 886 unspecified-consequence records; 6 stop-gained variants; 68 synonymous variants; 72 missense variants; 14 frameshift variants; 2 in-frame insertions; 5 in-frame deletions; 2 splice-region variants
- Prediction scores: 866 variants have prediction scores (82% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Ear-patella-short stature syndrome, neurodegenerative disease, lysosomal storage disease, kidney transplant, lung carcinoma, lung cancer, colorectal carcinoma, acute myeloid leukemia, cervical carcinoma, cervical cancer, cervical adenocarcinoma, rheumatoid arthritis.
Protein structure and variant hotspots
- Protein features: 1 domains; 1 binding sites; 6 post-translational modification sites.
- Structural context: 402 variants have structural context.
- 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 MCM5 variants
Examples include S2L, S2*, S2S, G3V, G3G, F4S, F4L, D5E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2L (p.Ser2Leu), 1000Genomes rs535953237, ExAC rs535953237, REVEL 0.32, MetaLR 0.15, Uncertain significance, not specified
- S2* (p.Ser2Ter), gnomAD 22-35400443-C-A, CADD 47.00
- S2S (p.Ser2Ser), rs201861668, gnomAD 22-35400444-G-A, CADD 14.70
- G3V (p.Gly3Val), ExAC rs775476754, gnomAD rs775476754, REVEL 0.50, MetaLR 0.38
- G3G (p.Gly3Gly), gnomAD 22-35400447-A-T, CADD 15.60
- F4S (p.Phe4Ser), gnomAD 22-35400449-T-C, REVEL 0.51, CADD 33.00
- F4L (p.Phe4Leu), gnomAD 22-35400450-C-G, REVEL 0.22, CADD 23.70
- D5E (p.Asp5Glu), gnomAD rs1477587333, REVEL 0.21, MetaLR 0.41
- D5N (p.Asp5Asn), rs1280481672, ClinGen CA411356330, ClinVar RCV001968877, TOPMed rs1280481672, REVEL 0.50, MetaLR 0.56, Uncertain significance, not provided
- D5D (p.Asp5Asp), gnomAD 22-35400453-C-T, CADD 15.80
- D6H (p.Asp6His), ExAC rs762908562, gnomAD rs762908562, REVEL 0.14, MetaLR 0.18
- D6E (p.Asp6Glu), gnomAD 22-35400456-T-G, REVEL 0.19, CADD 16.70
- P7A (p.Pro7Ala), rs764150043, NCI-TCGA Cosmic COSV5334, cosmic curated COSV53346, ExAC rs764150043, REVEL 0.19, MetaLR 0.08, Variant assessed as somatic; moderate impact.
- P7L (p.Pro7Leu), ExAC rs751342425, gnomAD rs751342425, REVEL 0.10, MetaLR 0.09
- P7S (p.Pro7Ser), cosmic curated COSV10507, ExAC rs764150043, TOPMed rs764150043, gnomAD rs764150043, REVEL 0.14, MetaLR 0.10
- G8G (p.Gly8Gly), rs1293440847, gnomAD 22-35400462-C-T, CADD 16.90
- I9V (p.Ile9Val), ExAC rs761707670, TOPMed rs761707670, REVEL 0.04, MetaLR 0.02, Uncertain significance, not provided
- I9L (p.Ile9Leu), gnomAD 22-35400463-A-C, REVEL 0.10, CADD 21.80
- I9I (p.Ile9Ile), rs767484813, gnomAD 22-35400465-T-A, CADD 8.27
- F10L (p.Phe10Leu), TOPMed rs1932006401, gnomAD rs1932006401
- F10F (p.Phe10Phe), rs1932006401, gnomAD 22-35400468-C-T, CADD 18.20
- Y11* (p.Tyr11Ter), ExAC rs766162364, TOPMed rs766162364, gnomAD rs766162364, CADD 33.00
- Y11L (p.Tyr11Leu), rs1569061941, gnomAD 22-35400463-A-AT, CADD 33.00
- Y11C (p.Tyr11Cys), gnomAD 22-35400470-A-G, REVEL 0.26, CADD 25.70
- Y11Y (p.Tyr11Tyr), rs750075192, gnomAD 22-35400471-C-T, CADD 15.70
- S12S (p.Ser12Ser), rs755770217, gnomAD 22-35400474-C-T, CADD 16.00
- D13G (p.Asp13Gly), rs141005002, ClinGen CA10204896, ClinVar RCV002000321, ClinVar RCV004042422, REVEL 0.27, MetaLR 0.14, Uncertain significance, not provided; not specified
- D13N (p.Asp13Asn), 1000Genomes rs575116718, TOPMed rs575116718, gnomAD rs575116718, REVEL 0.17, MetaLR 0.28
- D13Y (p.Asp13Tyr), 1000Genomes rs575116718, TOPMed rs575116718, gnomAD rs575116718, REVEL 0.47, MetaLR 0.34
- D13D (p.Asp13Asp), gnomAD 22-35400477-C-T, CADD 15.70
- S14C (p.Ser14Cys), 1000Genomes rs537676845, REVEL 0.23, MetaLR 0.14
- S14N (p.Ser14Asn), 1000Genomes rs557612451, TOPMed rs557612451, gnomAD rs557612451, REVEL 0.14, MetaLR 0.04
- S14T (p.Ser14Thr), 1000Genomes rs557612451, TOPMed rs557612451, gnomAD rs557612451, REVEL 0.12, MetaLR 0.06
- S14S (p.Ser14Ser), rs1322976871, gnomAD 22-35400480-C-T, CADD 15.90
- F15S (p.Phe15Ser), gnomAD 22-35400482-T-C, REVEL 0.43, CADD 28.90
- G16A (p.Gly16Ala), gnomAD rs1218665637, REVEL 0.22, MetaLR 0.06
- G16G (p.Gly16Gly), gnomAD 22-35400486-G-C, CADD 12.80
- G17D (p.Gly17Asp), gnomAD rs1290401825, REVEL 0.30, MetaLR 0.05, Uncertain significance, not specified
- G17V (p.Gly17Val), gnomAD rs1290401825, REVEL 0.17, MetaLR 0.06
- D18V (p.Asp18Val), ExAC rs753315401, TOPMed rs753315401, gnomAD rs753315401, REVEL 0.21, MetaLR 0.14
- D18N (p.Asp18Asn), gnomAD 22-35400490-G-A, REVEL 0.13, CADD 25.60
- D18D (p.Asp18Asp), rs1260649916, gnomAD 22-35400492-C-T, CADD 12.40
- A19T (p.Ala19Thr), gnomAD rs1484701979
- p.Ala19 Gln20insArgGlyAspAla, gnomAD 22-35400484-G-GGG, CADD 22.60
- A19S (p.Ala19Ser), gnomAD 22-35400493-G-T, REVEL 0.01, CADD 6.83
- Q20E (p.Gln20Glu), gnomAD 22-35400496-C-G, REVEL 0.10, CADD 12.20
- A21V (p.Ala21Val), rs577905878, ClinGen CA10204898, ClinVar RCV003558057, 1000Genomes rs577905878, Uncertain significance, not provided
- A21A (p.Ala21Ala), rs1182832079, gnomAD 22-35400501-C-G, CADD 14.50
- D22E (p.Asp22Glu), TOPMed rs1164779153, gnomAD rs1164779153, REVEL 0.01, MetaLR 0.04
- D22N (p.Asp22Asn), ExAC rs778264069, TOPMed rs778264069, gnomAD rs778264069, REVEL 0.13, MetaLR 0.09
- D22V (p.Asp22Val), gnomAD rs1422590605, REVEL 0.28, MetaLR 0.14
- D22del (p.Asp22del), gnomAD 22-35400500-CCGA-, CADD 22.70
- D22D (p.Asp22Asp), rs1164779153, gnomAD 22-35400504-C-T, CADD 5.26
- E23D (p.Glu23Asp), TOPMed rs1380987629, gnomAD rs1380987629, REVEL 0.03, MetaLR 0.04
- E23G (p.Glu23Gly), gnomAD 22-35400505-GA-G, CADD 32.00
- G24G (p.Gly24Gly), rs1012911132, gnomAD 22-35400510-G-T, CADD 9.88
- Q25E (p.Gln25Glu), gnomAD rs1296547517, REVEL 0.13, MetaLR 0.05
- Q25R (p.Gln25Arg), Ensembl rs1932009387
- Q25P (p.Gln25Pro), gnomAD 22-35400507-GGGGC, CADD 32.00
- Q25H (p.Gln25His), gnomAD 22-35400513-G-C, REVEL 0.08, CADD 21.20
- A26S (p.Ala26Ser), ExAC rs747305293, gnomAD rs747305293
- A26T (p.Ala26Thr), NCI-TCGA Cosmic COSV5334, cosmic curated COSV53346, Variant assessed as somatic; moderate impact.
- A26V (p.Ala26Val), TOPMed rs1932009617, REVEL 0.05, MetaLR 0.03
- A26A (p.Ala26Ala), rs1429706131, gnomAD 22-35400516-C-G, CADD 14.40
- R27C (p.Arg27Cys), TOPMed rs1213676370, gnomAD rs1213676370, REVEL 0.13, MetaLR 0.04, Uncertain significance
- R27G (p.Arg27Gly), rs1213676370, ClinGen CA411356479, ClinVar RCV003848213, TOPMed rs1213676370, REVEL 0.12, MetaLR 0.04, Uncertain significance, not provided
- R27H (p.Arg27His), cosmic curated COSV53347, Ensembl rs367630495, REVEL 0.09, MetaLR 0.04
- R27S (p.Arg27Ser), cosmic curated COSV99332, TOPMed rs1213676370, gnomAD rs1213676370, Uncertain significance
- K28R (p.Lys28Arg), 1000Genomes rs200623346, ESP rs200623346, ExAC rs200623346, TOPMed rs200623346, Uncertain significance
- K28T (p.Lys28Thr), rs200623346, ClinGen CA10204901, ClinVar RCV002952726, ClinVar RCV004067185, REVEL 0.08, MetaLR 0.05, Uncertain significance, not specified; not provided
- K28del (p.Lys28del), gnomAD 22-35400519-CAAA-, CADD 21.70
- K28N (p.Lys28Asn), gnomAD 22-35400521-AATCG, CADD 31.00
- S29W (p.Ser29Trp), NCI-TCGA Cosmic COSV9933, cosmic curated COSV99331, Variant assessed as somatic; moderate impact.
- p.Ser29 Gln30del, gnomAD 22-35400523-TCGCA, CADD 22.40
- S29L (p.Ser29Leu), gnomAD 22-35400524-C-T, REVEL 0.07, CADD 23.20
- Q30E (p.Gln30Glu), cosmic curated COSV99332, gnomAD rs1932010519, REVEL 0.07, MetaLR 0.04
- Q30Q (p.Gln30Gln), rs1601749372, gnomAD 22-35400528-G-A, CADD 13.50
- L31P (p.Leu31Pro), gnomAD 22-35400530-T-C, REVEL 0.27, CADD 26.40
- R33K (p.Arg33Lys), gnomAD rs1381169659, REVEL 0.02, MetaLR 0.01
- R34C (p.Arg34Cys), gnomAD rs1932010959, REVEL 0.23, MetaLR 0.07
- R34L (p.Arg34Leu), TOPMed rs1016247988, REVEL 0.20, MetaLR 0.03
- R34P (p.Arg34Pro), TOPMed rs1016247988
- R34R (p.Arg34Arg), rs781462093, gnomAD 22-35400540-C-T, CADD 14.50
- F35L (p.Phe35Leu), Ensembl rs2145779419
- K36R (p.Lys36Arg), ESP rs143243348, ExAC rs143243348, TOPMed rs143243348, gnomAD rs143243348, REVEL 0.04, MetaLR 0.01
- K36K (p.Lys36Lys), rs769944763, gnomAD 22-35400546-G-A, CADD 15.40
- E37K (p.Glu37Lys), gnomAD rs1241732679, REVEL 0.34, MetaLR 0.05
- E37E (p.Glu37Glu), rs763956899, gnomAD 22-35400549-G-A, CADD 15.10
- F38L (p.Phe38Leu), TOPMed rs1447168504, gnomAD rs1447168504, REVEL 0.39, MetaLR 0.21
- F38F (p.Phe38Phe), rs1447168504, gnomAD 22-35400552-C-T, CADD 15.50
- L39P (p.Leu39Pro), gnomAD rs1932012110, REVEL 0.63, MetaLR 0.14
- L39R (p.Leu39Arg), rs1932012110, ClinGen CA411356647, ClinVar RCV002305207, Uncertain significance, not provided
- L39C (p.Leu39Cys), rs1315986075, gnomAD 22-35400551-TC-T, CADD 26.70
- L39L (p.Leu39Leu), gnomAD 22-35400555-G-A, CADD 14.10
- R40L (p.Arg40Leu), TOPMed rs972098548, gnomAD rs972098548
- R40Q (p.Arg40Gln), TOPMed rs972098548, gnomAD rs972098548, REVEL 0.25, MetaLR 0.08
- R40R (p.Arg40Arg), gnomAD 22-35400558-G-T, CADD 13.60
- Q41R (p.Gln41Arg), Ensembl rs11541533
- Y42* (p.Tyr42Ter), ExAC rs763140069, gnomAD rs763140069, CADD 38.00
- Y42N (p.Tyr42Asn), gnomAD 22-35400562-T-A, REVEL 0.30, CADD 32.00
- Y42Y (p.Tyr42Tyr), gnomAD 22-35400564-C-T, CADD 13.70
- R43L (p.Arg43Leu), rs2145779463, ClinGen CA411356729, NCI-TCGA Cosmic COSV5334, cosmic curated COSV53348, Uncertain significance, not provided
- R43R (p.Arg43Arg), gnomAD 22-35400567-A-C, CADD 9.90
- V44G (p.Val44Gly), gnomAD rs1932012907, REVEL 0.18, MetaLR 0.02
- V44L (p.Val44Leu), gnomAD 22-35400568-G-C, REVEL 0.07, CADD 21.80
- V44V (p.Val44Val), gnomAD 22-35400570-G-A, CADD 16.00
- G45del (p.Gly45del), rs753571968, gnomAD 22-35400570-GGGC-, CADD 22.80
- G45G (p.Gly45Gly), gnomAD 22-35400573-C-A, CADD 15.00
- T46A (p.Thr46Ala), TOPMed rs1932013138, gnomAD rs1932013138, REVEL 0.32, MetaLR 0.05
- T46N (p.Thr46Asn), gnomAD rs1239577739
- T46S (p.Thr46Ser), gnomAD 22-35400574-A-T, REVEL 0.29, CADD 22.90
- T46T (p.Thr46Thr), rs1191942718, gnomAD 22-35400576-C-T, CADD 15.10
- D47N (p.Asp47Asn), gnomAD 22-35400577-G-A, REVEL 0.18, CADD 23.60
- R48H (p.Arg48His), ExAC rs768649710, gnomAD rs768649710, REVEL 0.15, MetaLR 0.18
- R48L (p.Arg48Leu), ExAC rs768649710, gnomAD rs768649710, REVEL 0.21, MetaLR 0.12
- R48S (p.Arg48Ser), TOPMed rs1309249103, gnomAD rs1309249103, REVEL 0.21, MetaLR 0.08
- R48C (p.Arg48Cys), gnomAD 22-35400580-C-T, REVEL 0.29, CADD 32.00
- R48R (p.Arg48Arg), rs1417037758, gnomAD 22-35400582-C-T, CADD 14.30
- T49A (p.Thr49Ala), TOPMed rs1932013952, REVEL 0.10, MetaLR 0.05
- T49M (p.Thr49Met), Ensembl rs1932014054
- T49T (p.Thr49Thr), rs199930889, gnomAD 22-35400585-G-T, CADD 10.20
- G50G (p.Gly50Gly), rs774428208, gnomAD 22-35400588-C-A, CADD 14.80
- F51L (p.Phe51Leu), rs761898056, ClinGen CA10204910, ClinVar RCV001988273, ClinVar RCV004042440, REVEL 0.10, MetaLR 0.09, Uncertain significance, not provided; not specified
- F51F (p.Phe51Phe), rs376131731, gnomAD 22-35400591-C-T, CADD 14.90
- T52A (p.Thr52Ala), TOPMed rs954865384, gnomAD rs954865384, REVEL 0.16, MetaLR 0.03
- T52I (p.Thr52Ile), rs1932014776, ClinGen CA411356914, ClinVar RCV004315865, TOPMed rs1932014776, REVEL 0.09, MetaLR 0.06, Uncertain significance, not specified
- T52T (p.Thr52Thr), gnomAD 22-35400594-C-T, CADD 12.40
- F53C (p.Phe53Cys), gnomAD 22-35400596-T-G, REVEL 0.26, CADD 32.00
- F53L (p.Phe53Leu), gnomAD 22-35400597-C-A, REVEL 0.14, CADD 25.10
- K54E (p.Lys54Glu), gnomAD 22-35400598-A-G, REVEL 0.29, CADD 24.20
- K54R (p.Lys54Arg), gnomAD 22-35400599-A-G, REVEL 0.16, CADD 23.20
- Y55* (p.Tyr55Ter), rs1379856222, gnomAD 22-35400602-AC-A, CADD 29.90
- R56K (p.Arg56Lys), gnomAD rs1415258592
- R56M (p.Arg56Met), gnomAD 22-35400605-G-T, REVEL 0.58, CADD 36.00
- R56R (p.Arg56Arg), gnomAD 22-35403207-G-A, CADD 14.50
- E58K (p.Glu58Lys), TOPMed rs1932111212, REVEL 0.33, MetaLR 0.26
- L59P (p.Leu59Pro), rs4645737, gnomAD 22-35401373-T-C, CADD 7.59
- L59L (p.Leu59Leu), rs1166059720, gnomAD 22-35401384-T-C, CADD 5.65
- R61W (p.Arg61Trp), 1000Genomes rs118180933, ESP rs118180933, ExAC rs118180933, TOPMed rs118180933, REVEL 0.37, MetaLR 0.12, Uncertain significance, not provided
- R61R (p.Arg61Arg), rs1405395718, gnomAD 22-35401410-A-G, CADD 1.02
- R61S (p.Arg61Ser), rs1405395718, gnomAD 22-35401410-A-C, CADD 0.89
- R61A (p.Arg61Ala), rs1569063218, gnomAD 22-35403216-C-CA, CADD 33.00
- R61Q (p.Arg61Gln), gnomAD 22-35403221-G-A, REVEL 0.31, CADD 23.50
- H62R (p.His62Arg), TOPMed rs201362121, gnomAD rs201362121, REVEL 0.36, MetaLR 0.20
- H62Y (p.His62Tyr), gnomAD 22-35401393-C-T, CADD 3.49
- H62L (p.His62Leu), gnomAD 22-35401394-A-T, CADD 1.23
- Y63C (p.Tyr63Cys), Ensembl rs1932111835
- Y63* (p.Tyr63Ter), gnomAD 22-35403227-AC-A, CADD 27.30
- Y63Y (p.Tyr63Tyr), rs770611705, gnomAD 22-35403228-C-T, CADD 11.90
- N64H (p.Asn64His), rs1180611774, ClinGen CA411358955, cosmic curated COSV99331, ClinVar RCV003546893, REVEL 0.15, MetaLR 0.04, Uncertain significance, not specified; not provided
- N64Y (p.Asn64Tyr), TOPMed rs1180611774, gnomAD rs1180611774, REVEL 0.24, MetaLR 0.04, Uncertain significance
- N64S (p.Asn64Ser), gnomAD 22-35403230-A-G, REVEL 0.09, CADD 17.80
- N64N (p.Asn64Asn), rs776452657, gnomAD 22-35403231-C-T, CADD 11.90
- L65M (p.Leu65Met), gnomAD 22-35401396-C-A, CADD 3.81
- L65A (p.Leu65Ala), gnomAD 22-35401396-C-CT, CADD 5.79
- L65L (p.Leu65Leu), gnomAD 22-35401398-G-A, CADD 4.85
- G66W (p.Gly66Trp), gnomAD 22-35401420-G-T, CADD 5.74
- G66A (p.Gly66Ala), rs1932047142, gnomAD 22-35401421-G-C, CADD 7.51
- G66G (p.Gly66Gly), gnomAD 22-35401422-G-T, CADD 8.62
- E67D (p.Glu67Asp), rs759149447, ExAC rs759149447, TOPMed rs759149447, gnomAD rs759149447, REVEL 0.07, MetaLR 0.18, Uncertain significance, not provided
- E67S (p.Glu67Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E67A (p.Glu67Ala), gnomAD 22-35401389-TGA-T, CADD 2.24
- E67* (p.Glu67Ter), gnomAD 22-35401390-G-T, CADD 2.61
- E67K (p.Glu67Lys), gnomAD 22-35403238-G-A, REVEL 0.24, CADD 22.80
- E67E (p.Glu67Glu), rs759149447, gnomAD 22-35403240-G-A, CADD 9.37
- Y68Y (p.Tyr68Tyr), rs2145780445, gnomAD 22-35401413-C-T, CADD 7.99
- p.Tyr68dup, gnomAD 22-35403240-G-GTA, CADD 19.50
- Y68F (p.Tyr68Phe), gnomAD 22-35403242-A-T, REVEL 0.13, CADD 22.40
- W69R (p.Trp69Arg), ExAC rs774927495, gnomAD rs774927495, REVEL 0.51, MetaLR 0.02
- W69C (p.Trp69Cys), gnomAD 22-35403246-G-T, REVEL 0.34, CADD 25.60
- I70S (p.Ile70Ser), rs1173639492, gnomAD 22-35401382-CATTG, CADD 3.52
- V72A (p.Val72Ala), ExAC rs763729545, gnomAD rs763729545, REVEL 0.63, MetaLR 0.49
- V72M (p.Val72Met), ExAC rs762377865, gnomAD rs762377865, REVEL 0.43, MetaLR 0.19, Uncertain significance, not specified
- V72V (p.Val72Val), gnomAD 22-35403255-G-T, CADD 13.10
- E73G (p.Glu73Gly), gnomAD 22-35403257-A-G, REVEL 0.38, CADD 26.80
- M74I (p.Met74Ile), NCI-TCGA Cosmic COSV5334, cosmic curated COSV53348, Variant assessed as somatic; moderate impact.
- M74R (p.Met74Arg), TOPMed rs1932113196
- M74V (p.Met74Val), ExAC rs750883580, gnomAD rs750883580, REVEL 0.09, MetaLR 0.02
- D76A (p.Asp76Ala), ExAC rs756691015, TOPMed rs756691015, Uncertain significance
- D76V (p.Asp76Val), rs756691015, ClinGen CA10204958, ClinVar RCV002299803, ExAC rs756691015, REVEL 0.55, MetaLR 0.16, Uncertain significance, not provided
Public MCM5 analysis runs
- MCM5 analysis run — MCM5 (1,055 variants) — completed 2026-08-20