ORC1 (Q13415) variants and mutations
ORC1 (also known as Q13415) is a human protein-coding gene encoding an origin recognition complex subunit 1 protein. It helps mark replication origins and assemble the prereplication complex needed to license DNA replication once per cell cycle. Biallelic pathogenic variants cause Meier-Gorlin syndrome, characterized by severe growth restriction, microtia, and absent or small patellae. This analysis covers 1,350 ORC1 variants and mutations. Of these, 66% have computational variant effect predictions. Disease context includes Ear-patella-short stature syndrome, neurodegenerative disease, and Meier-Gorlin syndrome. Example ORC1 variants include A2T, A2V, and A2P.
Variant analysis overview
- Gene: ORC1
- Protein: Q13415
- UniProt accession: Q13415
- Organism: Homo sapiens
- Variants analyzed: 1350
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 1,077 unspecified-consequence records; 173 missense variants; 66 synonymous variants; 8 stop-gained variants; 5 in-frame deletions; 16 frameshift variants; 2 splice-region variants; 1 protein altering variant; 2 substitution
- Prediction scores: 891 variants have prediction scores (66% 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, Meier-Gorlin syndrome, hereditary disease, microcephalic primordial dwarfism, neoplasm, cervical carcinoma, cervical cancer, prostate adenocarcinoma, hepatocellular carcinoma, breast cancer, cancer.
Protein structure and variant hotspots
- Protein features: 1 domains; 7 binding sites; 12 post-translational modification sites.
- Structural context: 306 variants have structural context.
- PTM context: 13 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 ORC1 variants
Examples include A2T, A2V, A2P, A2A, A2G, H3L, H3P, H3R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2T (p.Ala2Thr), gnomAD rs1264010214
- A2V (p.Ala2Val), TOPMed rs1348967000, gnomAD rs1348967000, MetaLR 0.25, MetaSVM -0.73
- A2P (p.Ala2Pro), rs781526529, gnomAD 13-40793242-G-C, REVEL 0.38, CADD 23.30
- A2A (p.Ala2Ala), rs573033866, gnomAD 13-40793244-T-C, CADD 7.02
- A2G (p.Ala2Gly), rs749585613, gnomAD 13-40793279-C-G, REVEL 0.54, CADD 23.70
- H3L (p.His3Leu), ESP rs146333732, ExAC rs146333732, TOPMed rs146333732, gnomAD rs146333732, Uncertain significance
- H3P (p.His3Pro), rs146333732, ClinGen CA853702, ClinVar RCV003028741, ESP rs146333732, AlphaMissense 0.08, MetaLR 0.07, Uncertain significance, not provided
- H3R (p.His3Arg), ESP rs146333732, ExAC rs146333732, TOPMed rs146333732, gnomAD rs146333732, MetaLR 0.37, MetaSVM -0.61, Uncertain significance
- Y4C (p.Tyr4Cys), cosmic curated COSV99933
- Y4H (p.Tyr4His), TOPMed rs1647746522, MetaLR 0.26, MetaSVM -0.76
- P5A (p.Pro5Ala), TOPMed rs1356760932, gnomAD rs1356760932
- P5R (p.Pro5Arg), ExAC rs751628938, gnomAD rs751628938, MetaLR 0.63, MetaSVM 0.08
- P5T (p.Pro5Thr), rs751757710, gnomAD 13-40793239-C-A, REVEL 0.31, CADD 23.30
- P5S (p.Pro5Ser), rs751757710, gnomAD 13-40793239-C-T, REVEL 0.24, CADD 18.30
- P5P (p.Pro5Pro), rs757399947, gnomAD 13-40793241-T-A, CADD 4.02
- T6A (p.Thr6Ala), TOPMed rs1215224327, gnomAD rs1215224327
- T6I (p.Thr6Ile), TOPMed rs1385792341, gnomAD rs1385792341
- T6Q (p.Thr6Gln), NCI-TCGA TCGA novel, MetaLR 0.26, MetaSVM -0.79, Variant assessed as somatic; high impact.
- K9Q (p.Lys9Gln), gnomAD rs1178780076, MetaLR 0.34, MetaSVM -0.57
- K12N (p.Lys12Asn), NCI-TCGA Cosmic COSV9993, cosmic curated COSV99933, Variant assessed as somatic; moderate impact.
- K12R (p.Lys12Arg), TOPMed rs1647742931, MetaLR 0.59, MetaSVM 0.28, Uncertain significance, Inborn genetic diseases
- T13A (p.Thr13Ala), TOPMed rs1161193587, gnomAD rs1161193587
- T13S (p.Thr13Ser), TOPMed rs1348794249, gnomAD rs1348794249, MetaLR 0.74, MetaSVM 0.65
- T13P (p.Thr13Pro), gnomAD 13-40793266-A-C, REVEL 0.51, CADD 24.50
- T13T (p.Thr13Thr), gnomAD 13-40793268-A-C, CADD 0.19
- Y14* (p.Tyr14Ter), TOPMed rs1290247294
- S15L (p.Ser15Leu), cosmic curated COSV99056, ExAC rs765136006, gnomAD rs765136006, MetaLR 0.81, MetaSVM 0.86
- S15Y (p.Ser15Tyr), gnomAD 13-40793234-C-A, REVEL 0.23, CADD 15.60
- S15C (p.Ser15Cys), rs1881570937, gnomAD 13-40793234-C-G, REVEL 0.22, CADD 18.90
- S15S (p.Ser15Ser), gnomAD 13-40793235-C-T, CADD 9.74
- W16C (p.Trp16Cys), TOPMed rs1176379478, gnomAD rs1176379478
- V17I (p.Val17Ile), ExAC rs759344414, TOPMed rs759344414, gnomAD rs759344414, MetaLR 0.31, MetaSVM -0.65
- V17V (p.Val17Val), rs1392943139, gnomAD 13-40799073-A-T, CADD 0.23
- G18R (p.Gly18Arg), rs2138039631, gnomAD 13-40793272-G-A, REVEL 0.87, CADD 25.10
- G18A (p.Gly18Ala), rs1566121208, gnomAD 13-40799057-G-C, REVEL 0.47, CADD 31.00
- p.Gly20 Thr21del, rs767135599, gnomAD 13-40799057-GAGGT, CADD 16.40
- G18E (p.Gly18Glu), rs1566121208, gnomAD 13-40799057-G-A, REVEL 0.88, CADD 32.00
- G18V (p.Gly18Val), rs1566121215, gnomAD 13-40799058-AG-A, CADD 26.10
- G18G (p.Gly18Gly), gnomAD 13-40799058-A-T, CADD 11.20
- G18D (p.Gly18Asp), gnomAD 13-40799060-G-A, REVEL 0.85, CADD 24.10
- R19S (p.Arg19Ser), rs3087473, ClinGen CA853695, ClinVar RCV000246237, ClinVar RCV000347437, AlphaMissense 0.19, MetaLR 0.06, Benign/Likely benign, not specified; not provided; Meier-Gorlin syndrome 1
- P20A (p.Pro20Ala), cosmic curated COSV57122
- P20T (p.Pro20Thr), Ensembl rs1647741184, MetaLR 0.81, MetaSVM 0.89
- P20S (p.Pro20Ser), gnomAD 13-40799122-C-T, REVEL 0.63, CADD 25.10
- D23E (p.Asp23Glu), ExAC rs770603666, gnomAD rs770603666, MetaLR 0.60, MetaSVM 0.12
- D23Y (p.Asp23Tyr), rs759454598, gnomAD 13-40799092-G-T, REVEL 0.88, CADD 27.90
- D23V (p.Asp23Val), gnomAD 13-40799093-A-T, REVEL 0.92, CADD 26.40
- R24* (p.Arg24Ter), rs1263248699, NCI-TCGA Cosmic COSV9993, cosmic curated COSV99933, TOPMed rs1263248699, AlphaMissense 0.13, MetaLR 0.19, Variant assessed as somatic; high impact.
- R24G (p.Arg24Gly), TOPMed rs1263248699, gnomAD rs1263248699
- R24Q (p.Arg24Gln), rs1224929934, ClinGen CA340366669, ClinVar RCV003376987, gnomAD rs1224929934, AlphaMissense 0.08, MetaLR 0.05, Likely benign, Inborn genetic diseases
- L26V (p.Leu26Val), Ensembl rs972590050, MetaLR 0.21, MetaSVM -0.81
- L26L (p.Leu26Leu), rs2138045646, gnomAD 13-40799076-G-C, CADD 6.15
- H27R (p.His27Arg), TOPMed rs1248787400, gnomAD rs1248787400
- H27Y (p.His27Tyr), Ensembl rs2147948317, MetaLR 0.75, MetaSVM 0.83
- Y28C (p.Tyr28Cys), rs1289766387, ClinGen CA340366642, ClinVar RCV004502319, TOPMed rs1289766387, AlphaMissense 0.07, MetaLR 0.14, Uncertain significance, Inborn genetic diseases
- Q29K (p.Gln29Lys), cosmic curated COSV99933
- Q29R (p.Gln29Arg), ExAC rs746678541, MetaLR 0.97, MetaSVM 1.07
- Q29E (p.Gln29Glu), gnomAD 13-40793248-C-G, REVEL 0.35, CADD 16.50
- Q29* (p.Gln29Ter), rs1448259297, gnomAD 13-40793248-C-T, CADD 36.00
- Q29P (p.Gln29Pro), gnomAD 13-40799114-A-C, REVEL 0.79, CADD 26.70
- T30P (p.Thr30Pro), ExAC rs772643977, TOPMed rs772643977, gnomAD rs772643977, MetaLR 0.14, MetaSVM -0.96
- T30T (p.Thr30Thr), gnomAD 13-40799079-C-G, CADD 0.10
- T30I (p.Thr30Ile), rs121908536, gnomAD 13-40799096-C-T, REVEL 0.75, CADD 24.70
- Y31C (p.Tyr31Cys), ExAC rs771602254, gnomAD rs771602254, MetaLR 0.77, MetaSVM 0.75
- R32G (p.Arg32Gly), TOPMed rs1224668630, gnomAD rs1224668630, MetaLR 0.73, MetaSVM 0.69
- R32W (p.Arg32Trp), rs540292884, gnomAD 13-40799134-C-T, REVEL 0.55, CADD 23.90
- R32Q (p.Arg32Gln), rs201647638, gnomAD 13-40799135-G-A, REVEL 0.32, CADD 20.30
- E33* (p.Glu33Ter), rs1049381810, Ensembl rs1049381810, Variant assessed as somatic; high impact.
- M34I (p.Met34Ile), TOPMed rs1647705169, MetaLR 0.88, MetaSVM 0.76
- M34K (p.Met34Lys), rs752415542, gnomAD 13-40799096-CAATG, CADD 27.70
- M34V (p.Met34Val), rs1881774173, gnomAD 13-40799098-A-G, REVEL 0.20, CADD 8.98
- M34R (p.Met34Arg), rs199737843, gnomAD 13-40799099-T-G, REVEL 0.50, CADD 23.10
- M34T (p.Met34Thr), rs121908533, gnomAD 13-40799111-T-C, REVEL 0.91, CADD 24.90
- C35F (p.Cys35Phe), rs894548961, ClinGen CA22527114, ClinVar RCV002906342, TOPMed rs894548961, AlphaMissense 0.08, MetaLR 0.02, Uncertain significance, Inborn genetic diseases
- C35S (p.Cys35Ser), TOPMed rs894548961, MetaLR 0.80, MetaSVM 0.82, Uncertain significance
- C35Y (p.Cys35Tyr), rs772613660, gnomAD 13-40799069-G-A, REVEL 0.72, CADD 23.50
- C35W (p.Cys35Trp), gnomAD 13-40799070-T-G, REVEL 0.67, CADD 23.00
- V36A (p.Val36Ala), NCI-TCGA TCGA novel, MetaLR 0.68, MetaSVM 0.51, Variant assessed as somatic; moderate impact.
- V36L (p.Val36Leu), rs1881774568, gnomAD 13-40799104-G-T, REVEL 0.77, CADD 25.00
- V36G (p.Val36Gly), gnomAD 13-40799105-T-G, REVEL 0.86, CADD 25.60
- V36V (p.Val36Val), rs1206882399, gnomAD 13-40799106-G-A, CADD 7.02
- K37E (p.Lys37Glu), rs762809317, gnomAD 13-40799101-A-G, REVEL 0.90, CADD 26.20
- K37I (p.Lys37Ile), gnomAD 13-40799102-A-T, REVEL 0.90, CADD 29.00
- T38I (p.Thr38Ile), ExAC rs758529447, TOPMed rs758529447, gnomAD rs758529447, MetaLR 0.84, MetaSVM 0.72
- T38M (p.Thr38Met), rs764024928, gnomAD 13-40799117-C-T, REVEL 0.79, CADD 25.80
- T38T (p.Thr38Thr), rs41396747, gnomAD 13-40799118-G-A, CADD 1.22
- E39D (p.Glu39Asp), rs1647704264, ClinGen CA340366552, ClinVar RCV003035327, gnomAD rs1647704264, AlphaMissense 0.09, MetaLR 0.11, Uncertain significance, not provided
- E39Q (p.Glu39Gln), TOPMed rs1216068347, gnomAD rs1216068347, MetaLR 0.76, MetaSVM 0.56
- C41G (p.Cys41Gly), Ensembl rs1048133661
- C41R (p.Cys41Arg), Ensembl rs1048133661
- C41Y (p.Cys41Tyr), rs758838019, gnomAD 13-40799150-G-A, REVEL 0.79, CADD 25.70
- S42F (p.Ser42Phe), ExAC rs201614313, gnomAD rs201614313, MetaLR 0.25, MetaSVM -0.82
- T43S (p.Thr43Ser), cosmic curated COSV10585
- T43T (p.Thr43Thr), rs376634191, gnomAD 13-40799145-C-A, CADD 0.41
- T43I (p.Thr43Ile), gnomAD 13-40799162-C-T, REVEL 0.42, CADD 19.10
- T43Q (p.Thr43Gln), rs1348599886, gnomAD 13-40799199-TAC-T, CADD 29.30
- E44K (p.Glu44Lys), cosmic curated COSV57121, TOPMed rs1448307641, gnomAD rs1448307641, MetaLR 0.74, MetaSVM 0.70
- I45T (p.Ile45Thr), ExAC rs759449048, TOPMed rs759449048, gnomAD rs759449048
- I45V (p.Ile45Val), rs1156296838, gnomAD 13-40793245-A-G, REVEL 0.21, CADD 6.67
- I45I (p.Ile45Ile), rs1360586910, gnomAD 13-40793247-C-T, CADD 8.04
- I47V (p.Ile47Val), TOPMed rs1246556960
- Q48H (p.Gln48His), cosmic curated COSV57123
- Q48R (p.Gln48Arg), TOPMed rs1647702679, gnomAD rs1647702679, MetaLR 0.21, MetaSVM -0.90
- I49V (p.Ile49Val), ExAC rs766094257, gnomAD rs766094257
- G50S (p.Gly50Ser), gnomAD 13-40799137-G-A, REVEL 0.47, CADD 21.20
- G50R (p.Gly50Arg), gnomAD 13-40799137-G-C, REVEL 0.85, CADD 25.10
- G50V (p.Gly50Val), gnomAD 13-40799138-G-T, REVEL 0.86, CADD 26.00
- G50G (p.Gly50Gly), rs560300254, gnomAD 13-40799139-C-T, CADD 9.20
- Q51E (p.Gln51Glu), rs182707743, ClinGen CA853672, ClinVar RCV001100137, ClinVar RCV001414367, AlphaMissense 0.08, MetaLR 0.51, Conflicting interpretations, Meier-Gorlin syndrome 1; not provided
- Q51H (p.Gln51His), Ensembl rs764805666
- Q51R (p.Gln51Arg), 1000Genomes rs76966719, ExAC rs76966719, TOPMed rs76966719
- F52L (p.Phe52Leu), rs776411120, gnomAD 13-40799089-T-C, REVEL 0.12, CADD 17.10
- F52D (p.Phe52Asp), rs756522093, gnomAD 13-40799112-G-GCA, CADD 32.00
- F52S (p.Phe52Ser), gnomAD 13-40799180-T-C, REVEL 0.64, CADD 24.80
- V53L (p.Val53Leu), Ensembl rs1647701178
- V53W (p.Val53Trp), rs1881780569, gnomAD 13-40799171-AG-A, CADD 34.00
- V53M (p.Val53Met), rs1310621949, gnomAD 13-40799173-G-A, REVEL 0.32, CADD 23.40
- V53A (p.Val53Ala), rs1881780968, gnomAD 13-40799174-T-C, REVEL 0.37, CADD 21.90
- L54L (p.Leu54Leu), gnomAD 13-40799128-C-T, CADD 9.15
- L54V (p.Leu54Val), gnomAD 13-40799128-C-G, REVEL 0.12, CADD 15.90
- L54R (p.Leu54Arg), rs1451525627, gnomAD 13-40799129-T-G, REVEL 0.52, CADD 23.60
- L54F (p.Leu54Phe), rs144656633, gnomAD 13-40799140-C-T, REVEL 0.17, CADD 9.36
- I55V (p.Ile55Val), gnomAD 13-40799215-A-G, REVEL 0.16, CADD 11.90
- I55T (p.Ile55Thr), gnomAD 13-40799216-T-C, REVEL 0.46, CADD 21.90
- I55I (p.Ile55Ile), rs572717478, gnomAD 13-40799217-C-T, CADD 4.26
- I55F (p.Ile55Phe), rs755209386, gnomAD 13-40799224-A-T, REVEL 0.79, CADD 25.10
- G57A (p.Gly57Ala), Ensembl rs1557587126
- G57R (p.Gly57Arg), TOPMed rs1647700697
- G57T (p.Gly57Thr), rs1324907002, gnomAD 13-40799174-T-TTA, CADD 28.50
- G57V (p.Gly57Val), rs1450707170, gnomAD 13-40799175-G-GGT, CADD 32.00
- G57S (p.Gly57Ser), rs1206371362, gnomAD 13-40799176-G-A, REVEL 0.87, CADD 29.30
- G57G (p.Gly57Gly), rs1057519112, gnomAD 13-40799178-C-A, CADD 10.60
- D58E (p.Asp58Glu), 1000Genomes rs200774303, ExAC rs200774303, TOPMed rs200774303, gnomAD rs200774303
- D58H (p.Asp58His), rs1566121276, gnomAD 13-40799125-G-C, REVEL 0.13, CADD 13.30
- D58D (p.Asp58Asp), rs1881775884, gnomAD 13-40799127-C-T, CADD 8.33
- D58N (p.Asp58Asn), rs539373322, gnomAD 13-40799146-G-A, REVEL 0.31, CADD 21.50
- D59N (p.Asp59Asn), TOPMed rs925076603, gnomAD rs925076603
- D60E (p.Asp60Glu), TOPMed rs1647699644
- D60G (p.Asp60Gly), TOPMed rs1346706870, gnomAD rs1346706870, MetaLR 0.54, MetaSVM 0.16
- E61K (p.Glu61Lys), cosmic curated COSV99933, MetaLR 0.45, MetaSVM -0.46
- N62H (p.Asn62His), NCI-TCGA Cosmic COSV5712, cosmic curated COSV57121, Variant assessed as somatic; moderate impact.
- N62K (p.Asn62Lys), rs2524192840, ClinGen CA340366291, ClinVar RCV003219963, Uncertain significance, Inborn genetic diseases
- N62Y (p.Asn62Tyr), TOPMed rs1318374818, gnomAD rs1318374818, MetaLR 0.83, MetaSVM 0.84
- N62D (p.Asn62Asp), rs1298151723, gnomAD 13-40799221-A-G, REVEL 0.66, CADD 25.30
- N62S (p.Asn62Ser), rs1414286965, gnomAD 13-40799222-A-G, REVEL 0.35, CADD 22.90
- N62N (p.Asn62Asn), gnomAD 13-40799235-C-T, CADD 9.61
- P63A (p.Pro63Ala), gnomAD rs1162398068
- P63L (p.Pro63Leu), TOPMed rs978048793, gnomAD rs978048793
- Y64C (p.Tyr64Cys), ESP rs367621213, TOPMed rs367621213, gnomAD rs367621213, REVEL 0.85, CADD 29.00
- Y64F (p.Tyr64Phe), gnomAD 13-40799165-A-T, REVEL 0.36, CADD 19.80
- Y64Y (p.Tyr64Tyr), gnomAD 13-40799166-C-T, CADD 5.05
- A66S (p.Ala66Ser), gnomAD 13-40799209-G-T, REVEL 0.59, CADD 23.30
- A66V (p.Ala66Val), gnomAD 13-40799210-C-T, REVEL 0.85, CADD 24.50
- A66T (p.Ala66Thr), rs531611390, gnomAD 13-40799218-G-A, REVEL 0.68, CADD 26.10
- A66G (p.Ala66Gly), rs753868358, gnomAD 13-40799219-C-G, REVEL 0.58, CADD 23.20
- A66A (p.Ala66Ala), gnomAD 13-40799220-C-T, CADD 11.10
- K67T (p.Lys67Thr), TOPMed rs1260748024
- K67R (p.Lys67Arg), rs746560103, gnomAD 13-40799159-A-G, REVEL 0.23, CADD 19.80
- K67K (p.Lys67Lys), gnomAD 13-40799160-G-A, CADD 11.40
- K67E (p.Lys67Glu), rs1330537054, gnomAD 13-40799194-A-G, REVEL 0.50, CADD 22.60
- E70K (p.Glu70Lys), cosmic curated COSV57122
- E70Q (p.Glu70Gln), NCI-TCGA Cosmic COSV5712, NCI-TCGA Cosmic COSV9993, cosmic curated COSV99933, MetaLR 0.34, MetaSVM -0.59, Variant assessed as somatic; moderate impact.
- L71L (p.Leu71Leu), gnomAD 13-40799214-A-G, CADD 1.05
- L71F (p.Leu71Phe), rs550585368, gnomAD 13-40799242-C-T, REVEL 0.64, CADD 25.60
- F72L (p.Phe72Leu), NCI-TCGA Cosmic COSV5712, cosmic curated COSV57122, Variant assessed as somatic; moderate impact.
- F72V (p.Phe72Val), ExAC rs757581044, gnomAD rs757581044, MetaLR 0.13, MetaSVM -0.95
- F72F (p.Phe72Phe), gnomAD 13-40799190-C-T, CADD 12.60
- E73G (p.Glu73Gly), cosmic curated COSV99933
- E73K (p.Glu73Lys), rs373671398, ClinGen CA853662, cosmic curated COSV57122, ClinVar RCV001527375, AlphaMissense 0.14, MetaLR 0.64, Pathogenic, Meier-Gorlin syndrome 1
- E73A (p.Glu73Ala), gnomAD 13-40799231-A-C, REVEL 0.77, CADD 26.80
- E73D (p.Glu73Asp), rs778193187, gnomAD 13-40799232-G-T, REVEL 0.70, CADD 24.20
- D74=, NCI-TCGA Cosmic COSV5712, Variant assessed as somatic; low impact.
- D74N (p.Asp74Asn), gnomAD rs1647696865
- D74V (p.Asp74Val), TOPMed rs1360700383, gnomAD rs1360700383
- D74Y (p.Asp74Tyr), cosmic curated COSV99933, MetaLR 0.41, MetaSVM -0.43
- D75N (p.Asp75Asn), gnomAD rs1294503158
- S76R (p.Ser76Arg), rs774319330, gnomAD 13-40799205-T-A, REVEL 0.56, CADD 17.70
- S76* (p.Ser76Ter), rs2138045987, gnomAD 13-40799237-C-G, CADD 37.00
- D77V (p.Asp77Val), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10085, MetaLR 0.42, MetaSVM -0.41, Variant assessed as somatic; moderate impact.
- P78A (p.Pro78Ala), rs368625910, ClinGen CA853641, ClinVar RCV004502312, ESP rs368625910, AlphaMissense 0.06, MetaLR 0.37, Uncertain significance, Inborn genetic diseases
Public ORC1 analysis runs
- ORC1 analysis run — ORC1 (1,350 variants) — completed 2026-08-20