CEP290 (Centrosomal protein of 290 kDa) variants and mutations
CEP290 (also known as Centrosomal protein of 290 kDa) is a human protein-coding gene encoding a centrosomal protein of 290 kDa protein. It organizes the transition zone of primary and sensory cilia and is essential for ciliary protein trafficking, especially in photoreceptors. Biallelic pathogenic variants cause a broad ciliopathy spectrum including Leber congenital amaurosis, Joubert syndrome, and nephronophthisis-related disease. This analysis covers 3,422 CEP290 variants and mutations. Of these, 81% have computational variant effect predictions. Disease context includes Joubert syndrome 5, Leber congenital amaurosis 10, and Senior-Loken syndrome 6. Example CEP290 variants include M1I, M1K, and M1V.
Variant analysis overview
- Gene: CEP290
- Protein: Centrosomal protein of 290 kDa
- UniProt accession: O15078
- Organism: Homo sapiens
- Variants analyzed: 3422
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 3,098 unspecified-consequence records; 1 stop retained variant; 1 stop lost; 76 synonymous variants; 13 stop-gained variants; 173 missense variants; 44 frameshift variants; 8 in-frame deletions; 5 in-frame insertions; 3 splice-region variants; 3 substitution
- Prediction scores: 2,763 variants have prediction scores (81% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Joubert syndrome 5, Leber congenital amaurosis 10, Senior-Loken syndrome 6, Meckel syndrome, type 4, Meckel syndrome, Leber congenital amaurosis, Bardet-Biedl syndrome 14, Joubert syndrome, Senior-Loken syndrome, Joubert syndrome with oculorenal defect, CEP290-related ciliopathy, Bardet-Biedl syndrome.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable CEP290 variants
Examples include M1I, M1K, M1V, P2L, P2S, N4D, N4K, N4T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs773525033, ClinGen CA6712932, ClinVar RCV001956388, ClinVar RCV005002725, MetaLR 0.84, MetaSVM 0.80, Pathogenic/Likely pathogenic, Joubert syndrome 5; Leber congenital amaurosis 10; Senior-Loken syndrome 6
- M1K (p.Met1Lys), rs368984997, ClinGen CA6712933, ClinVar RCV001091344, ClinVar RCV001862693, MetaLR 0.82, MetaSVM 0.82, Pathogenic, CEP290-related ciliopathy
- M1V (p.Met1Val), rs2040644756, ClinGen CA385990599, ClinVar RCV001091345, ClinVar RCV002555951, MetaLR 0.82, MetaSVM 0.82, Pathogenic/Likely pathogenic, Meckel-Gruber syndrome; Joubert syndrome; Nephronophthisis
- P2L (p.Pro2Leu), TOPMed rs2040643955, REVEL 0.29, CADD 24.60, Uncertain significance, Inborn genetic diseases
- P2S (p.Pro2Ser), rs1064795491, ClinGen CA16619603, ClinVar RCV000478865, ClinVar RCV001373838, REVEL 0.08, CADD 22.60, Uncertain significance, Meckel-Gruber syndrome; Nephronophthisis; Joubert syndrome
- N4D (p.Asn4Asp), rs997653455, ClinGen CA241168932, ClinVar RCV001916478, ClinVar RCV004733414, REVEL 0.12, CADD 22.20, Conflicting interpretations, Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14
- N4K (p.Asn4Lys), ExAC rs748657371, TOPMed rs748657371, gnomAD rs748657371, REVEL 0.05, CADD 16.30, Likely benign
- N4T (p.Asn4Thr), ExAC rs770326046, TOPMed rs770326046, gnomAD rs770326046, REVEL 0.11, CADD 14.90, Likely benign, Inborn genetic diseases
- I5L (p.Ile5Leu), rs1046797710, ClinGen CA241168931, ClinVar RCV002588971, ClinVar RCV004733516, REVEL 0.07, CADD 17.30, Uncertain significance, Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis
- I5M (p.Ile5Met), Ensembl rs929739343, REVEL 0.16, CADD 23.40, Uncertain significance, Leber congenital amaurosis
- I5R (p.Ile5Arg), rs1434632102, ClinGen CA385990527, ClinVar RCV003889641, Ensembl rs1434632102, REVEL 0.29, CADD 26.20, Uncertain significance, Retinal dystrophy
- I5T (p.Ile5Thr), rs1434632102, ClinGen CA385990528, ClinVar RCV000988893, Ensembl rs1434632102, REVEL 0.26, CADD 22.90, Likely pathogenic, Joubert syndrome 1
- W7C (p.Trp7Cys), rs62635288, ClinGen CA227962, ClinVar RCV000001398, ClinVar RCV000086283, REVEL 0.74, CADD 28.30, Likely pathogenic, CEP290-related ciliopathy
- E9Q (p.Glu9Gln), Ensembl rs2138306475
- I10V (p.Ile10Val), gnomAD rs2040642730, REVEL 0.04, CADD 13.40, Uncertain significance, CEP290-related disorder
- M11I (p.Met11Ile), gnomAD rs1165769352
- M11V (p.Met11Val), rs185939120, ClinGen CA6712929, ClinVar RCV000294199, ClinVar RCV000297891, REVEL 0.08, CADD 23.20, Uncertain significance, Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6
- V13D (p.Val13Asp), rs2501865235, ClinGen CA385990383, ClinVar RCV003040160, ClinVar RCV003319535, Uncertain significance, CEP290-related ciliopathy
- D14G (p.Asp14Gly), rs2138306044, ClinGen CA385990371, ClinVar RCV001591914, Ensembl rs2138306044, AlphaMissense 0.33, MetaLR 0.59, Uncertain significance, Leber congenital amaurosis 10
- D14N (p.Asp14Asn), rs769179397, ClinGen CA6712928, ClinVar RCV001973404, ExAC rs769179397, REVEL 0.25, CADD 24.00, Uncertain significance, Nephronophthisis; Meckel-Gruber syndrome; Joubert syndrome
- P15A (p.Pro15Ala), rs1425716932, ClinGen CA385990362, ClinVar RCV000658664, ClinVar RCV001199652, REVEL 0.39, CADD 25.70, Conflicting interpretations, Retinitis pigmentosa; not provided
- P15T (p.Pro15Thr), TOPMed rs1425716932, gnomAD rs1425716932, REVEL 0.44, CADD 26.30, Pathogenic
- D16H (p.Asp16His), rs2040641439, ClinGen CA385990350, ClinVar RCV002050132, Ensembl rs2040641439, AlphaMissense 0.24, MetaLR 0.71, Uncertain significance, Joubert syndrome; Nephronophthisis; Meckel-Gruber syndrome
- D17A (p.Asp17Ala), rs1182703361, ClinGen CA385990331, ClinVar RCV002278929, ClinVar RCV003101599, REVEL 0.05, CADD 21.20, Uncertain significance, Nephronophthisis; Meckel-Gruber syndrome; Joubert syndrome
- D17N (p.Asp17Asn), NCI-TCGA Cosmic COSV9989, cosmic curated COSV99898, Variant assessed as somatic; moderate impact.
- R20C (p.Arg20Cys), rs779867970, ClinGen CA6712926, NCI-TCGA Cosmic COSV5712, cosmic curated COSV57124, REVEL 0.31, CADD 28.00, Uncertain significance, Meckel-Gruber syndrome; Nephronophthisis; Joubert syndrome
- R20H (p.Arg20His), cosmic curated COSV99898, TOPMed rs2040640720, REVEL 0.21, CADD 22.00
- Q21* (p.Gln21Ter), Ensembl rs2040640355
- E22K (p.Glu22Lys), NCI-TCGA Cosmic COSV5712, cosmic curated COSV57124, Variant assessed as somatic; moderate impact.
- E23* (p.Glu23Ter), NCI-TCGA Cosmic COSV9989, Variant assessed as somatic; high impact.
- E23V (p.Glu23Val), ExAC rs757919599, gnomAD rs757919599, REVEL 0.36, CADD 32.00
- A25S (p.Ala25Ser), ExAC rs757196729, gnomAD rs757196729, REVEL 0.28, CADD 26.20, Uncertain significance, Leber congenital amaurosis
- A25T (p.Ala25Thr), ExAC rs757196729, gnomAD rs757196729, REVEL 0.30, CADD 26.40
- A25V (p.Ala25Val), rs1356762631, ClinGen CA385990213, cosmic curated COSV57124, ClinVar RCV003063071, REVEL 0.34, CADD 32.00, Uncertain significance, Joubert syndrome; Nephronophthisis; Meckel-Gruber syndrome
- D26E (p.Asp26Glu), rs2040639110, ClinGen CA385990193, ClinVar RCV002305195, Uncertain significance, Nephronophthisis; Meckel-Gruber syndrome; Joubert syndrome
- D26N (p.Asp26Asn), rs2501863127, ClinGen CA385990210, ClinVar RCV004528720, REVEL 0.12, CADD 23.50, Uncertain significance, CEP290-related disorder
- N27D (p.Asn27Asp), rs753760503, ClinGen CA6712920, ClinVar RCV001048254, ClinVar RCV001832450, REVEL 0.10, CADD 21.00, Uncertain significance, Senior-Loken syndrome 6; Leber congenital amaurosis 10; Meckel syndrome, type 4
- L29* (p.Leu29Ter), NCI-TCGA Cosmic COSV9989, cosmic curated COSV99897, Variant assessed as somatic; high impact.
- S31F (p.Ser31Phe), rs1378106199, ClinGen CA385990127, ClinVar RCV001279938, gnomAD rs1378106199, AlphaMissense 0.12, MetaLR 0.41, Uncertain significance, Leber congenital amaurosis
- S31P (p.Ser31Pro), ExAC rs765211180, gnomAD rs765211180, REVEL 0.33, CADD 23.40, Uncertain significance, not provided
- L32S (p.Leu32Ser), TOPMed rs1390112820, gnomAD rs1390112820, REVEL 0.36, CADD 24.40
- S33C (p.Ser33Cys), ExAC rs751721358, TOPMed rs751721358, gnomAD rs751721358
- S33F (p.Ser33Phe), ExAC rs751721358, TOPMed rs751721358, gnomAD rs751721358, REVEL 0.29, CADD 24.40
- K34M (p.Lys34Met), rs574089816, ClinGen CA6712916, ClinVar RCV001307629, 1000Genomes rs574089816, REVEL 0.26, CADD 28.40, Uncertain significance, Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis
- K34N (p.Lys34Asn), Ensembl rs2138303674
- K34Q (p.Lys34Gln), rs2040637392, ClinGen CA385990090, ClinVar RCV002297344, TOPMed rs2040637392, AlphaMissense 0.12, MetaLR 0.63, Uncertain significance, Nephronophthisis; Meckel-Gruber syndrome; Joubert syndrome
- V35A (p.Val35Ala), rs2501853647, ClinGen CA385990020, ClinVar RCV003887497, REVEL 0.24, CADD 25.60, Uncertain significance, not provided
- V35G (p.Val35Gly), rs2501853647, ClinGen CA385990018, ClinVar RCV003334468, ClinVar RCV004529628, REVEL 0.28, CADD 33.00, VUS-high, Joubert syndrome 5
- E36* (p.Glu36Ter), rs868347260, ClinGen CA241168621, ClinVar RCV003783595, TOPMed rs868347260, CADD 37.00, Pathogenic
- E36K (p.Glu36Lys), TOPMed rs868347260, gnomAD rs868347260, REVEL 0.20, CADD 22.80, Pathogenic
- V37A (p.Val37Ala), gnomAD rs1378182544, REVEL 0.15, CADD 15.90
- S42R (p.Ser42Arg), gnomAD rs1200899018, REVEL 0.11, CADD 18.20
- Q45H (p.Gln45His), rs2138298764, ClinGen CA385989902, ClinVar RCV001992390, Ensembl rs2138298764, REVEL 0.14, CADD 21.20, Uncertain significance, Nephronophthisis; Meckel-Gruber syndrome; Joubert syndrome
- Q45P (p.Gln45Pro), ExAC rs755840362, gnomAD rs755840362, REVEL 0.10, CADD 18.00
- Q45R (p.Gln45Arg), ExAC rs755840362, gnomAD rs755840362, REVEL 0.12, CADD 21.80
- E46D (p.Glu46Asp), NCI-TCGA Cosmic COSV5712, cosmic curated COSV57122, Variant assessed as somatic; moderate impact.
- E46K (p.Glu46Lys), rs1018550969, ClinGen CA241168610, ClinVar RCV002031068, TOPMed rs1018550969, REVEL 0.41, CADD 28.60, Uncertain significance, Nephronophthisis; Meckel-Gruber syndrome; Joubert syndrome
- I49M (p.Ile49Met), rs2501850748, ClinGen CA385989858, ClinVar RCV002675547, REVEL 0.07, CADD 18.90, Uncertain significance, Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis
- H50D (p.His50Asp), TOPMed rs878853363, gnomAD rs878853363, REVEL 0.38, CADD 24.20, Uncertain significance, Leber congenital amaurosis
- H50R (p.His50Arg), rs2138298302, ClinGen CA385989846, ClinVar RCV001997207, ClinVar RCV005002709, REVEL 0.28, CADD 21.80, Uncertain significance, Joubert syndrome 5; Leber congenital amaurosis 10; Senior-Loken syndrome 6
- H50Y (p.His50Tyr), rs878853363, ClinGen CA10581687, ClinVar RCV000225409, ClinVar RCV001854802, REVEL 0.38, CADD 25.90, Pathogenic, CEP290-related ciliopathy
- L51F (p.Leu51Phe), rs1264332374, ClinGen CA385989834, ClinVar RCV000636993, ClinVar RCV002507078, REVEL 0.40, CADD 27.20, Uncertain significance, Meckel-Gruber syndrome; Joubert syndrome; Nephronophthisis
- L51I (p.Leu51Ile), TOPMed rs1264332374, gnomAD rs1264332374, REVEL 0.27, CADD 25.80, Uncertain significance
- F52L (p.Phe52Leu), NCI-TCGA TCGA novel, TOPMed rs1169026059, Variant assessed as somatic; moderate impact.
- R53S (p.Arg53Ser), Ensembl rs2040620232
- I54T (p.Ile54Thr), ExAC rs767353670, gnomAD rs767353670, REVEL 0.35, CADD 23.80
- Q56* (p.Gln56Ter), rs1592706963, ClinGen CA385989775, ClinVar RCV000823106, Ensembl rs1592706963, CADD 41.00, Pathogenic
- Q56L (p.Gln56Leu), TOPMed rs1350378313, gnomAD rs1350378313, REVEL 0.59, CADD 27.20, Uncertain significance, Leber congenital amaurosis
- M59L (p.Met59Leu), TOPMed rs1272110007, gnomAD rs1272110007
- M59V (p.Met59Val), TOPMed rs1272110007, gnomAD rs1272110007, REVEL 0.30, CADD 23.10
- A63P (p.Ala63Pro), ExAC rs777331611, gnomAD rs777331611
- A63V (p.Ala63Val), rs769705891, ClinGen CA6712880, ClinVar RCV001320459, ClinVar RCV001830339, REVEL 0.15, CADD 22.20, Uncertain significance, Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis
- Q64* (p.Gln64Ter), rs1166981120, ClinGen CA385989437, ClinVar RCV001972739, gnomAD rs1166981120, CADD 38.00, Pathogenic
- Q64E (p.Gln64Glu), rs1166981120, NCI-TCGA Cosmic COSV9989, cosmic curated COSV99898, gnomAD rs1166981120, REVEL 0.23, CADD 20.20, Pathogenic
- Q64H (p.Gln64His), rs965922201, ClinGen CA241167352, ClinVar RCV002269696, ClinVar RCV005002814, REVEL 0.34, CADD 24.20, Uncertain significance, not provided; Meckel syndrome, type 4; Senior-Loken syndrome 6
- E65* (p.Glu65Ter), NCI-TCGA Cosmic COSV5712, cosmic curated COSV57122, Variant assessed as somatic; high impact.
- V66M (p.Val66Met), ExAC rs748129496, gnomAD rs748129496, REVEL 0.20, CADD 25.40
- A69S (p.Ala69Ser), TOPMed rs2040522634, REVEL 0.31, CADD 23.20
- A69V (p.Ala69Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L70F (p.Leu70Phe), Ensembl rs2138266557, REVEL 0.27, CADD 23.00
- L70M (p.Leu70Met), ExAC rs754757278, gnomAD rs754757278
- L70W (p.Leu70Trp), TOPMed rs2040522347
- E71K (p.Glu71Lys), TOPMed rs2040522225, REVEL 0.32, CADD 24.60
- E72* (p.Glu72Ter), rs1292246271, ClinGen CA385989259, ClinVar RCV003041166, CADD 37.00, Pathogenic
- E72D (p.Glu72Asp), rs750607382, ClinGen CA6712877, ClinVar RCV003092862, ClinVar RCV003161817, REVEL 0.29, CADD 24.00, Uncertain significance, Inborn genetic diseases; Joubert syndrome; Nephronophthisis
- E72K (p.Glu72Lys), NCI-TCGA Cosmic COSV5712, TOPMed rs1292246271, gnomAD rs1292246271, REVEL 0.28, CADD 25.10, Variant assessed as somatic; high impact.
- V73A (p.Val73Ala), TOPMed rs1361487879, REVEL 0.27, CADD 23.50
- V73E (p.Val73Glu), TOPMed rs1361487879
- E74K (p.Glu74Lys), TOPMed rs1243132131, gnomAD rs1243132131
- E74Q (p.Glu74Gln), TOPMed rs1243132131, gnomAD rs1243132131, REVEL 0.21, CADD 24.50
- K75E (p.Lys75Glu), rs779010679, ClinGen CA6712876, cosmic curated COSV57125, ClinVar RCV000988892, REVEL 0.25, CADD 23.80, Likely pathogenic, CEP290-related ciliopathy
- A76T (p.Ala76Thr), rs373913704, ClinGen CA233682, cosmic curated COSV99898, ClinVar RCV000723892, REVEL 0.29, CADD 25.80, Conflicting interpretations, Inborn genetic diseases; Joubert syndrome; Nephronophthisis
- G77E (p.Gly77Glu), TOPMed rs1437952702, gnomAD rs1437952702, REVEL 0.38, CADD 23.80
- E79Q (p.Glu79Gln), Ensembl rs2040520314
- K82N (p.Lys82Asn), rs761233532, ClinGen CA6712873, ClinVar RCV002958333, ClinVar RCV004733550, REVEL 0.25, CADD 25.20, Uncertain significance, Joubert syndrome; Nephronophthisis; Meckel-Gruber syndrome
- E84K (p.Glu84Lys), Ensembl rs2040519662, REVEL 0.33, CADD 35.00, Uncertain significance, Leber congenital amaurosis
- N85K (p.Asn85Lys), rs1490527042, ClinGen CA385988900, ClinVar RCV003442453, TOPMed rs1490527042, REVEL 0.10, CADD 17.10, Uncertain significance, not provided
- Q86* (p.Gln86Ter), NCI-TCGA TCGA novel, CADD 38.00, Variant assessed as somatic; high impact.
- Q86K (p.Gln86Lys), rs1004064531, ClinGen CA241166995, ClinVar RCV001236115, TOPMed rs1004064531, REVEL 0.10, CADD 21.40, Uncertain significance, Meckel-Gruber syndrome; Nephronophthisis; Joubert syndrome
- L87* (p.Leu87Ter), Ensembl rs2040499201, CADD 37.00
- T89S (p.Thr89Ser), TOPMed rs2040498872
- K90* (p.Lys90Ter), rs1057517886, ClinGen CA16042812, ClinVar RCV000413097, Ensembl rs1057517886, CADD 38.00, Likely pathogenic
- V91I (p.Val91Ile), gnomAD rs1294292132, REVEL 0.11, CADD 14.10
- M92V (p.Met92Val), rs951351175, ClinGen CA241166992, ClinVar RCV001113986, ClinVar RCV001113987, REVEL 0.23, CADD 20.90, Uncertain significance, Meckel syndrome, type 4; Bardet-Biedl syndrome 14; Leber congenital amaurosis 10
- E95* (p.Glu95Ter), Ensembl rs865927858, CADD 45.00
- E95K (p.Glu95Lys), cosmic curated COSV57126, Ensembl rs865927858, REVEL 0.32, CADD 26.70
- E97* (p.Glu97Ter), rs386834153, ClinGen CA144391, ClinVar RCV000050147, ClinVar RCV001053674, CADD 39.00, Pathogenic
- E97D (p.Glu97Asp), rs757402765, ClinGen CA385988618, ClinVar RCV001343117, ClinVar RCV005005189, REVEL 0.39, CADD 23.20, Uncertain significance, Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis
- E97Q (p.Glu97Gln), 1000Genomes rs386834153, ExAC rs386834153, TOPMed rs386834153, gnomAD rs386834153, REVEL 0.32, CADD 23.50, Pathogenic
- L98P (p.Leu98Pro), TOPMed rs2040497062, REVEL 0.45, CADD 27.20
- M100V (p.Met100Val), Ensembl rs2040376372
- A101T (p.Ala101Thr), ExAC rs781389594, gnomAD rs781389594
- Q102R (p.Gln102Arg), rs2501714367, ClinGen CA385987810, ClinVar RCV003799331, REVEL 0.21, CADD 22.20, Uncertain significance, Joubert syndrome; Nephronophthisis; Meckel-Gruber syndrome
- Q103* (p.Gln103Ter), rs752144368, ClinGen CA6712832, ClinVar RCV001386072, ClinVar RCV003469718, CADD 37.00, Pathogenic
- Q103P (p.Gln103Pro), ExAC rs766609759, gnomAD rs766609759, REVEL 0.22, CADD 20.20
- Q103R (p.Gln103Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A105V (p.Ala105Val), cosmic curated COSV58348, Ensembl rs2138217209
- G107E (p.Gly107Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R108* (p.Arg108Ter), rs1290241933, ClinGen CA385987715, ClinVar RCV000810939, ClinVar RCV001030763, CADD 35.00, Pathogenic
- R108Q (p.Arg108Gln), rs758781417, NCI-TCGA Cosmic COSV5835, cosmic curated COSV58351, ExAC rs758781417, REVEL 0.24, CADD 24.20, Uncertain significance, CEP290-related disorder
- D109G (p.Asp109Gly), NCI-TCGA Cosmic COSV5835, cosmic curated COSV58351, TOPMed rs2040374381, gnomAD rs2040374381, REVEL 0.51, CADD 27.80, Variant assessed as somatic; moderate impact.
- T110A (p.Thr110Ala), rs750018041, ClinGen CA385987696, ClinVar RCV001345219, ClinVar RCV001825909, REVEL 0.29, CADD 24.60, Uncertain significance, CEP290-related ciliopathy; Joubert syndrome; Meckel-Gruber syndrome
- T110I (p.Thr110Ile), ExAC rs764867143, gnomAD rs764867143, REVEL 0.28, CADD 25.20, Uncertain significance, Joubert syndrome 5; Senior-Loken syndrome 6; Bardet-Biedl syndrome 14
- T110P (p.Thr110Pro), ExAC rs750018041, gnomAD rs750018041, REVEL 0.38, CADD 25.60, Uncertain significance, Joubert syndrome 5; Senior-Loken syndrome 6; Bardet-Biedl syndrome 14
- R111Q (p.Arg111Gln), rs562747993, ClinGen CA6712827, NCI-TCGA Cosmic COSV5835, cosmic curated COSV58352, REVEL 0.29, CADD 26.20, Uncertain significance, Joubert syndrome; Nephronophthisis; Meckel-Gruber syndrome
- R111W (p.Arg111Trp), rs1051440600, ClinGen CA241165275, ClinVar RCV001239679, ClinVar RCV001828930, REVEL 0.49, CADD 24.50, Uncertain significance, Meckel-Gruber syndrome; Nephronophthisis; Joubert syndrome
- L113* (p.Leu113Ter), rs2040373653, ClinGen CA385987649, ClinVar RCV001202458, Ensembl rs2040373653, Pathogenic
- R114C (p.Arg114Cys), rs776101043, NCI-TCGA Cosmic COSV5834, cosmic curated COSV58349, ExAC rs776101043, REVEL 0.47, CADD 29.10, Variant assessed as somatic; moderate impact.
- R114H (p.Arg114His), rs150296134, ClinGen CA246817, cosmic curated COSV58354, ClinVar RCV000179538, REVEL 0.40, CADD 26.50, Conflicting interpretations, Inborn genetic diseases; Meckel-Gruber syndrome; Joubert syndrome
- R114P (p.Arg114Pro), 1000Genomes rs150296134, ESP rs150296134, ExAC rs150296134, TOPMed rs150296134, REVEL 0.48, CADD 26.40, Likely benign
- R114S (p.Arg114Ser), ExAC rs776101043, TOPMed rs776101043, gnomAD rs776101043
- N115D (p.Asn115Asp), rs140236736, ClinGen CA246815, ClinVar RCV000179537, ClinVar RCV001085617, REVEL 0.15, CADD 15.60, Conflicting interpretations, Meckel syndrome, type 4; Joubert syndrome 5; Leber congenital amaurosis 10
- N115K (p.Asn115Lys), rs2501711671, ClinGen CA385987618, ClinVar RCV002299078, ClinVar RCV005608692, Uncertain significance, Nephronophthisis; Meckel-Gruber syndrome; Joubert syndrome
- C118Y (p.Cys118Tyr), NCI-TCGA Cosmic COSV5835, cosmic curated COSV58354, Variant assessed as somatic; moderate impact.
- Q119* (p.Gln119Ter), rs2138215835, ClinGen CA385987566, ClinVar RCV001384356, Ensembl rs2138215835, CADD 36.00, Pathogenic
- Q119L (p.Gln119Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E121* (p.Glu121Ter), rs2138215714, ClinGen CA385987523, ClinVar RCV001961872, Ensembl rs2138215714, Pathogenic
- E121A (p.Glu121Ala), rs2040372439, ClinGen CA385987521, ClinVar RCV001340171, ClinVar RCV002486369, AlphaMissense 0.25, MetaLR 0.69, Uncertain significance, Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis
- E121G (p.Glu121Gly), rs2040372439, ClinGen CA385987518, ClinVar RCV001969992, TOPMed rs2040372439, REVEL 0.38, AlphaMissense 0.25, Uncertain significance, Joubert syndrome; Nephronophthisis; Meckel-Gruber syndrome
- Q123* (p.Gln123Ter), rs770126103, ClinGen CA6712821, ClinVar RCV001058714, ClinVar RCV001832529, CADD 36.00, Pathogenic
- L124* (p.Leu124Ter), TOPMed rs1311709485, CADD 35.00
- E125* (p.Glu125Ter), rs2040371663, ClinGen CA385987450, ClinVar RCV001267299, Ensembl rs2040371663, Pathogenic
- E125A (p.Glu125Ala), TOPMed rs2040371532
- E125K (p.Glu125Lys), rs2040371663, ClinGen CA385987454, ClinVar RCV003069739, ClinVar RCV004733575, REVEL 0.26, CADD 25.50, Uncertain significance, Joubert syndrome; Nephronophthisis; Meckel-Gruber syndrome
- Q126* (p.Gln126Ter), TOPMed rs1222421581, gnomAD rs1222421581, CADD 36.00, Uncertain significance
- Q126E (p.Gln126Glu), TOPMed rs1222421581, gnomAD rs1222421581, REVEL 0.25, CADD 23.00, Uncertain significance
- Q126K (p.Gln126Lys), rs1222421581, ClinGen CA385987437, ClinVar RCV002913871, ClinVar RCV004733542, REVEL 0.18, CADD 23.50, Uncertain significance, Joubert syndrome; Nephronophthisis; Meckel-Gruber syndrome
- Q126L (p.Gln126Leu), rs748429036, ClinGen CA6712819, ClinVar RCV001324490, ExAC rs748429036, REVEL 0.40, CADD 23.10, Uncertain significance, Joubert syndrome; Nephronophthisis; Meckel-Gruber syndrome
- K127E (p.Lys127Glu), ExAC rs781101346, TOPMed rs781101346, gnomAD rs781101346, Uncertain significance
- K127Q (p.Lys127Gln), rs781101346, ClinGen CA6712818, ClinVar RCV000732950, ClinVar RCV002535303, REVEL 0.28, CADD 25.40, Uncertain significance, Meckel-Gruber syndrome; Nephronophthisis; Joubert syndrome
- D128H (p.Asp128His), rs755112866, ClinGen CA6712817, ClinVar RCV002586586, ClinVar RCV004534126, REVEL 0.25, AlphaMissense 0.14, Uncertain significance, Inborn genetic diseases; Nephronophthisis; Meckel-Gruber syndrome
- D128N (p.Asp128Asn), ExAC rs755112866, TOPMed rs755112866, gnomAD rs755112866, REVEL 0.21, AlphaMissense 0.14, Uncertain significance, CEP290-related disorder
- D128Y (p.Asp128Tyr), rs755112866, ClinGen CA385987399, cosmic curated COSV58350, ClinVar RCV001299329, AlphaMissense 0.14, MetaLR 0.63, Uncertain significance, Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis
- R129G (p.Arg129Gly), rs2138214415, ClinGen CA385987377, ClinVar RCV002015329, Ensembl rs2138214415, REVEL 0.39, CADD 23.60, Uncertain significance, Nephronophthisis; Meckel-Gruber syndrome; Joubert syndrome
- E130G (p.Glu130Gly), rs2501709322, ClinGen CA385987346, ClinVar RCV002727123, REVEL 0.37, CADD 26.50, Uncertain significance, Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis
- L131F (p.Leu131Phe), ExAC rs780621500, TOPMed rs780621500, gnomAD rs780621500, REVEL 0.33, CADD 21.60, Likely benign
- L131W (p.Leu131Trp), TOPMed rs1024695999, gnomAD rs1024695999, REVEL 0.44, CADD 28.50
- E132K (p.Glu132Lys), TOPMed rs2040369291, gnomAD rs2040369291, REVEL 0.08, CADD 18.00
- D133N (p.Asp133Asn), NCI-TCGA Cosmic COSV5835, cosmic curated COSV58350, Ensembl rs1592693373, Variant assessed as somatic; moderate impact.
- M134I (p.Met134Ile), cosmic curated COSV10516, gnomAD rs1205221239, REVEL 0.14, CADD 12.90
- M134V (p.Met134Val), gnomAD rs1469416559, REVEL 0.11, CADD 15.00
- K136M (p.Lys136Met), Ensembl rs2138213876
- E137A (p.Glu137Ala), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10046, Variant assessed as somatic; moderate impact.
- L138S (p.Leu138Ser), gnomAD rs1355121435, REVEL 0.43, CADD 25.90
- L138V (p.Leu138Val), Ensembl rs1592693326
- K140E (p.Lys140Glu), ESP rs377409636, ExAC rs377409636, TOPMed rs377409636, gnomAD rs377409636, REVEL 0.31, CADD 26.70
- K140R (p.Lys140Arg), rs750776051, ClinGen CA6712813, ClinVar RCV002021620, ExAC rs750776051, REVEL 0.25, CADD 22.60, Uncertain significance, Nephronophthisis; Meckel-Gruber syndrome; Joubert syndrome
- E141* (p.Glu141Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K142N (p.Lys142Asn), NCI-TCGA Cosmic COSV5835, cosmic curated COSV58351, REVEL 0.44, CADD 24.80, Variant assessed as somatic; moderate impact.
- K143I (p.Lys143Ile), Ensembl rs910085555
- N145D (p.Asn145Asp), NCI-TCGA Cosmic COSV5835, cosmic curated COSV58350, Variant assessed as somatic; moderate impact.
- N145S (p.Asn145Ser), rs1261226265, ClinGen CA385987097, ClinVar RCV002583077, TOPMed rs1261226265, REVEL 0.28, CADD 25.20, Uncertain significance, Nephronophthisis; Meckel-Gruber syndrome; Joubert syndrome
- A149T (p.Ala149Thr), Ensembl rs2040046847, REVEL 0.18, CADD 23.30
- A149V (p.Ala149Val), ExAC rs779213141, gnomAD rs779213141, REVEL 0.20, CADD 24.10
- L150F (p.Leu150Phe), rs1162631374, ClinGen CA385986683, ClinVar RCV002780946, ClinVar RCV004733529, REVEL 0.17, CADD 29.10, Uncertain significance, Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis
- L150V (p.Leu150Val), NCI-TCGA TCGA novel, REVEL 0.07, CADD 23.40, Variant assessed as somatic; moderate impact.
- R151* (p.Arg151Ter), rs757641323, ClinGen CA6712782, ClinVar RCV000414162, ClinVar RCV000552078, CADD 42.00, Pathogenic
- R151L (p.Arg151Leu), cosmic curated COSV58355, ExAC rs753374614, TOPMed rs753374614, gnomAD rs753374614, REVEL 0.31, CADD 31.00, Uncertain significance
- R151Q (p.Arg151Gln), rs753374614, ClinGen CA6712781, NCI-TCGA Cosmic COSV5835, cosmic curated COSV58353, REVEL 0.17, CADD 27.90, Uncertain significance, Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis
- N152D (p.Asn152Asp), rs2040045927, ClinGen CA385986676, ClinVar RCV003024832, gnomAD rs2040045927, REVEL 0.09, CADD 25.30, Uncertain significance, Joubert syndrome; Nephronophthisis; Meckel-Gruber syndrome
Public CEP290 analysis runs
- CEP290 analysis run — CEP290 (3,422 variants) — completed 2026-08-21