RPE65 (Retinoid isomerohydrolase) variants and mutations
RPE65 (also known as Retinoid isomerohydrolase) is a human protein-coding gene encoding a retinoid isomerohydrolase protein. It regenerates 11-cis-retinoid chromophore in the retinal pigment epithelium, allowing visual pigments to recover after light exposure. Biallelic loss-of-function variants cause severe inherited retinal dystrophy, and RPE65-associated disease is treatable with approved gene-replacement therapy. This analysis covers 1,062 RPE65 variants and mutations. Of these, 82% have computational variant effect predictions. Disease context includes retinitis pigmentosa, Leber congenital amaurosis 2, and Leber congenital amaurosis. Example RPE65 variants include M1?, M1I, and M1T.
Variant analysis overview
- Gene: RPE65
- Protein: Retinoid isomerohydrolase
- UniProt accession: Q16518
- Organism: Homo sapiens
- Variants analyzed: 1062
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 829 unspecified-consequence records; 95 synonymous variants; 102 missense variants; 6 in-frame deletions; 12 frameshift variants; 6 splice-region variants; 2 stop-gained variants; 1 in-frame insertions; 9 substitution
- Prediction scores: 874 variants have prediction scores (82% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: retinitis pigmentosa, Leber congenital amaurosis 2, Leber congenital amaurosis, Retinal dystrophy, RPE65-related recessive retinopathy, retinitis pigmentosa 87 with choroidal involvement, autosomal recessive retinitis pigmentosa, hereditary disease, Stargardt disease, retinal disorder, Abnormality of the eye, inherited retinal dystrophy.
Protein structure and variant hotspots
- Protein features: 4 binding sites; 5 post-translational modification sites.
- PTM context: 8 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, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable RPE65 variants
Examples include M1?, M1I, M1T, S2Y, I3N, I3T, I3V, Q4*. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV9925, Variant assessed as somatic; high impact.
- M1I (p.Met1Ile), rs1357241537, ClinGen CA340750383, ClinVar RCV001379122, ClinVar RCV004801002, MutPred 0.99, Pathogenic/Likely pathogenic, Retinitis pigmentosa 20; Leber congenital amaurosis 2; Leber congenital amaurosi
- M1T (p.Met1Thr), rs281865285, ClinGen CA226537, ClinVar RCV000085190, ClinVar RCV001376504, MutPred 1.00, Likely pathogenic, RPE65-related recessive retinopathy
- S2Y (p.Ser2Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I3N (p.Ile3Asn), 1000Genomes rs534901182, ExAC rs534901182, TOPMed rs534901182, gnomAD rs534901182, REVEL 0.29, MetaLR 0.26
- I3T (p.Ile3Thr), 1000Genomes rs534901182, ExAC rs534901182, TOPMed rs534901182, gnomAD rs534901182, REVEL 0.37, MetaLR 0.24
- I3V (p.Ile3Val), rs777461552, ClinGen CA902661, ClinVar RCV001239510, ClinVar RCV001834093, REVEL 0.24, MetaLR 0.32, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- Q4* (p.Gln4Ter), rs748096417, ClinGen CA902659, ClinVar RCV003032078, ClinVar RCV003465900, CADD 39.00, Pathogenic
- Q4H (p.Gln4His), rs1645960147, ClinGen CA340750353, ClinVar RCV001090222, Ensembl rs1645960147, MutPred 0.54, Uncertain significance, not provided
- Q4R (p.Gln4Arg), Ensembl rs1557605458, REVEL 0.27, MetaLR 0.38
- E6* (p.Glu6Ter), rs1315607990, ClinGen CA340750344, ClinVar RCV004527500, CADD 36.00, Pathogenic
- E6K (p.Glu6Lys), TOPMed rs1315607990, REVEL 0.67, MetaLR 0.60
- H7Q (p.His7Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H7R (p.His7Arg), rs2523458658, ClinGen CA340750334, ClinVar RCV002301339, ClinVar RCV004817014, REVEL 0.71, MetaLR 0.87, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- P8A (p.Pro8Ala), gnomAD rs938458992, REVEL 0.68, MetaLR 0.87
- P8S (p.Pro8Ser), gnomAD rs938458992
- G10D (p.Gly10Asp), gnomAD rs1645960075, REVEL 0.53, MetaLR 0.82, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- G10S (p.Gly10Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Y12* (p.Tyr12Ter), rs1233702775, ClinGen CA340750300, ClinVar RCV003466257, gnomAD rs1233702775, CADD 36.00, Likely pathogenic
- K13E (p.Lys13Glu), rs758419556, ClinGen CA902633, ClinVar RCV003117086, ExAC rs758419556, REVEL 0.45, MetaLR 0.58, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- K13Q (p.Lys13Gln), rs758419556, ClinGen CA340750299, ClinVar RCV002624380, MutPred 0.44, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- F16S (p.Phe16Ser), Ensembl rs1645959974, Uncertain significance, not specified
- E17K (p.Glu17Lys), NCI-TCGA Cosmic COSV5201, Variant assessed as somatic; moderate impact.
- T18A (p.Thr18Ala), ExAC rs765691555, gnomAD rs765691555, REVEL 0.57, MetaLR 0.78
- T18S (p.Thr18Ser), rs1645959906, ClinGen CA340750230, ClinVar RCV001349633, Ensembl rs1645959906, REVEL 0.36, MetaLR 0.50, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- V19E (p.Val19Glu), rs1645959875, ClinGen CA340750218, ClinVar RCV001309761, Ensembl rs1645959875, MutPred 0.72, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- V19L (p.Val19Leu), gnomAD rs1645959896, REVEL 0.42, MetaLR 0.81
- V19M (p.Val19Met), rs1645959896, ClinGen CA340750220, ClinVar RCV003805986, ClinVar RCV004527467, MutPred 0.57, Likely pathogenic, RPE65-related recessive retinopathy
- E20K (p.Glu20Lys), rs755545288, ClinGen CA902631, ClinVar RCV001346164, ClinVar RCV001825925, REVEL 0.58, MetaLR 0.67, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- E21* (p.Glu21Ter), rs2523458378, ClinGen CA340750196, ClinVar RCV003061518, Pathogenic
- L22P (p.Leu22Pro), rs61751277, ClinGen CA226576, ClinVar RCV000085218, ClinVar RCV001218527, REVEL 0.71, MetaLR 0.76, Likely pathogenic, RPE65-related recessive retinopathy
- S23P (p.Ser23Pro), TOPMed rs1349861264, REVEL 0.32, MetaLR 0.39, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- S23Y (p.Ser23Tyr), Ensembl rs201587195
- S24L (p.Ser24Leu), rs893611409, TOPMed rs893611409, gnomAD rs893611409, REVEL 0.30, MetaLR 0.64, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- P25L (p.Pro25Leu), rs199683808, ClinGen CA902628, ClinVar RCV000504723, ClinVar RCV001250673, REVEL 0.90, MetaLR 0.87, Pathogenic, RPE65-related recessive retinopathy
- P25Q (p.Pro25Gln), ExAC rs199683808, TOPMed rs199683808, gnomAD rs199683808, Pathogenic
- P25R (p.Pro25Arg), ExAC rs199683808, TOPMed rs199683808, gnomAD rs199683808, REVEL 0.85, MetaLR 0.91, Pathogenic
- L26F (p.Leu26Phe), Ensembl rs1571174186, Uncertain significance, Leber congenital amaurosis
- L26P (p.Leu26Pro), ExAC rs766996940, gnomAD rs766996940, REVEL 0.63, MetaLR 0.76
- T27I (p.Thr27Ile), rs794727245, ClinGen CA241334, ClinVar RCV000175585, TOPMed rs794727245, REVEL 0.35, MetaLR 0.67, Uncertain significance, not provided
- T27R (p.Thr27Arg), TOPMed rs794727245, Uncertain significance
- A28D (p.Ala28Asp), rs2523458181, ClinGen CA340750093, ClinVar RCV003794729, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- A28S (p.Ala28Ser), rs1285702731, ClinGen CA340750099, ClinVar RCV003008953, MutPred 0.59, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- A28T (p.Ala28Thr), TOPMed rs1285702731, gnomAD rs1285702731, REVEL 0.36, MetaLR 0.55
- H29R (p.His29Arg), rs2523458159, ClinGen CA340750080, ClinVar RCV002289206, ClinVar RCV003097772, Uncertain significance, Retinitis pigmentosa 87 with choroidal involvement; Leber congenital amaurosis 2
- V30A (p.Val30Ala), gnomAD rs1373308880, REVEL 0.77, MetaLR 0.91
- V30G (p.Val30Gly), gnomAD rs1373308880, REVEL 0.94, MetaLR 0.94
- V30L (p.Val30Leu), rs1645959414, ClinGen CA340750065, ClinVar RCV002757256, TOPMed rs1645959414, MutPred 0.70, Uncertain significance, Inborn genetic diseases
- T31I (p.Thr31Ile), ExAC rs774306896, gnomAD rs774306896, REVEL 0.28, MetaLR 0.68
- G32C (p.Gly32Cys), rs768448761, ClinGen CA902623, NCI-TCGA Cosmic COSV5201, ClinVar RCV001380405, REVEL 0.96, MetaLR 1.00, Pathogenic, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- G32S (p.Gly32Ser), ExAC rs768448761, gnomAD rs768448761, REVEL 0.96, MetaLR 1.00, Pathogenic
- G32V (p.Gly32Val), rs61751278, ClinGen CA226594, ClinVar RCV000085234, TOPMed rs61751278, MutPred 0.97, not provided
- I34F (p.Ile34Phe), TOPMed rs1398705256, gnomAD rs1398705256, REVEL 0.71, MetaLR 0.80
- I34T (p.Ile34Thr), rs748456353, ClinGen CA902596, ClinVar RCV003091163, ExAC rs748456353, REVEL 0.95, MetaLR 0.95, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- L36F (p.Leu36Phe), rs371586530, ClinGen CA902594, ClinVar RCV001239945, ClinVar RCV001834109, REVEL 0.18, MetaLR 0.62, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- W37S (p.Trp37Ser), rs1557603965, ClinGen CA340749285, ClinVar RCV000754596, Ensembl rs1557603965, MutPred 0.73, Uncertain significance, Congenital isolated adrenocorticotropic hormone deficiency
- L38R (p.Leu38Arg), rs1645946362, ClinGen CA340749268, ClinVar RCV001073366, Ensembl rs1645946362, MutPred 0.87, Uncertain significance, Retinal dystrophy
- G40D (p.Gly40Asp), rs2523452284, ClinGen CA340749254, ClinVar RCV003133792, ClinVar RCV003778716, REVEL 0.99, MetaLR 0.99, Likely pathogenic, not provided; Retinitis pigmentosa 20; Leber congenital amaurosis 2
- G40S (p.Gly40Ser), rs61751281, ClinGen CA226491, ClinVar RCV000085155, ClinVar RCV000132582, REVEL 0.98, MetaLR 0.99, Pathogenic, RPE65-related recessive retinopathy
- S41T (p.Ser41Thr), ExAC rs756508097, gnomAD rs756508097, REVEL 0.68, MetaLR 0.66
- L42F (p.Leu42Phe), rs750724065, ClinGen CA902590, NCI-TCGA Cosmic COSV5201, ClinVar RCV001243775, REVEL 0.88, MetaLR 0.92, Likely pathogenic, RPE65-related recessive retinopathy
- R44* (p.Arg44Ter), rs368088025, ClinGen CA902588, ClinVar RCV000416243, ClinVar RCV000528380, CADD 38.00, Pathogenic, in LCA2
- R44L (p.Arg44Leu), rs61751282, ClinGen CA340749205, ClinVar RCV001973421, ClinVar RCV006453839, MutPred 0.87, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20; not specified
- R44P (p.Arg44Pro), rs61751282, ClinGen CA340749207, ClinVar RCV003088739, 1000Genomes rs61751282, REVEL 0.99, MetaLR 0.98, Pathogenic, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- R44Q (p.Arg44Gln), rs61751282, ClinGen CA226506, NCI-TCGA Cosmic COSV5201, ClinVar RCV000085166, REVEL 0.97, MetaLR 0.98, Pathogenic, RPE65-related recessive retinopathy
- C45R (p.Cys45Arg), rs1645946067, ClinVar RCV004586290, TOPMed rs1645946067, gnomAD rs1645946067, REVEL 0.61, MetaLR 0.82, Uncertain significance, not specified
- C45Y (p.Cys45Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G46E (p.Gly46Glu), rs1022487798, NCI-TCGA Cosmic COSV9925, Ensembl rs1022487798, MutPred 0.98, Likely pathogenic, RPE65-related recessive retinopathy
- P47S (p.Pro47Ser), NCI-TCGA Cosmic COSV5201, Variant assessed as somatic; moderate impact.
- G48E (p.Gly48Glu), rs2100831413, ClinGen CA340749160, ClinVar RCV001591854, ClinVar RCV003771781, MutPred 0.90, Likely pathogenic, RPE65-related recessive retinopathy
- L49R (p.Leu49Arg), TOPMed rs1011553769, gnomAD rs1011553769, REVEL 0.70, MetaLR 0.80
- F50S (p.Phe50Ser), NCI-TCGA Cosmic COSV5201, TOPMed rs1186660643, gnomAD rs1186660643, Uncertain significance, not specified
- F50Y (p.Phe50Tyr), TOPMed rs1186660643, gnomAD rs1186660643, REVEL 0.78, MetaLR 0.88
- E51A (p.Glu51Ala), Ensembl rs1645945889, REVEL 0.92, MetaLR 0.91
- V52D (p.Val52Asp), Ensembl rs892723493, REVEL 0.96, MetaLR 0.91
- G53A (p.Gly53Ala), ExAC rs763536294, TOPMed rs763536294, gnomAD rs763536294, REVEL 0.88, MetaLR 0.94, Uncertain significance
- G53E (p.Gly53Glu), rs763536294, ClinGen CA902587, ClinVar RCV002890357, ExAC rs763536294, REVEL 0.84, MetaLR 0.93, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- G53V (p.Gly53Val), rs763536294, ClinGen CA340749110, ClinVar RCV001914725, ExAC rs763536294, MutPred 0.68, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- S54A (p.Ser54Ala), TOPMed rs930635180, gnomAD rs930635180, REVEL 0.28, MetaLR 0.49
- S54C (p.Ser54Cys), TOPMed rs1268808384, gnomAD rs1268808384, REVEL 0.52, MetaLR 0.80
- S54F (p.Ser54Phe), NCI-TCGA Cosmic COSV5201, Variant assessed as somatic; moderate impact.
- S54Y (p.Ser54Tyr), TOPMed rs1268808384, gnomAD rs1268808384, REVEL 0.57, MetaLR 0.82, Uncertain significance, Inborn genetic diseases
- E55D (p.Glu55Asp), ESP rs375272714, ExAC rs375272714, TOPMed rs375272714, gnomAD rs375272714, REVEL 0.47, MetaLR 0.45, Likely benign
- P56S (p.Pro56Ser), rs1193374066, ClinGen CA340749095, ClinVar RCV003118341, Ensembl rs1193374066, MutPred 0.35, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- F57L (p.Phe57Leu), rs2100831318, ClinGen CA340749084, ClinVar RCV001970390, Ensembl rs2100831318, MutPred 0.78, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- F57S (p.Phe57Ser), rs2523451761, ClinGen CA340749087, ClinVar RCV002281669, Pathogenic, Retinitis pigmentosa 20
- H59Y (p.His59Tyr), NCI-TCGA Cosmic COSV5201, Variant assessed as somatic; moderate impact.
- L60P (p.Leu60Pro), rs1266217912, UniProt VAR 071672, gnomAD rs1266217912, REVEL 0.87, MetaLR 0.89, Pathogenic, Leber congenital amaurosis
- F61C (p.Phe61Cys), NCI-TCGA Cosmic COSV5201, Variant assessed as somatic; moderate impact.
- G63R (p.Gly63Arg), rs1645945643, ClinGen CA340749045, ClinVar RCV001250679, Ensembl rs1645945643, MutPred 0.92, Likely pathogenic, Leber congenital amaurosis 2
- Q64* (p.Gln64Ter), rs1645945599, ClinGen CA340749039, ClinVar RCV001250680, ClinVar RCV005253768, Pathogenic
- L67R (p.Leu67Arg), rs1344724754, ClinGen CA340749010, ClinVar RCV001380404, ClinVar RCV003469648, REVEL 0.98, MetaLR 0.94, Pathogenic, RPE65-related recessive retinopathy
- H68P (p.His68Pro), rs1557603862, ClinGen CA340749000, ClinVar RCV000754598, Ensembl rs1557603862, MutPred 0.86, Uncertain significance, Congenital isolated adrenocorticotropic hormone deficiency
- H68Q (p.His68Gln), rs2523451589, ClinGen CA340748994, ClinVar RCV003304820, Uncertain significance, Inborn genetic diseases
- H68Y (p.His68Tyr), rs61752866, ClinGen CA226523, ClinVar RCV000085179, ClinVar RCV003466999, REVEL 0.93, MetaLR 0.92, Likely pathogenic, RPE65-related recessive retinopathy
- K69E (p.Lys69Glu), gnomAD rs1343988525, REVEL 0.83, MetaLR 0.89
- K69N (p.Lys69Asn), ExAC rs774650221, gnomAD rs774650221, REVEL 0.69, MetaLR 0.89
- F70G (p.Phe70Gly), rs281865287, ClinGen CA226524, ClinVar RCV000085180, Ensembl rs281865287, not provided
- F70S (p.Phe70Ser), rs1645945363, ClinGen CA340748969, ClinVar RCV001268583, ClinVar RCV005225342, MutPred 0.88, Likely pathogenic, Retinitis pigmentosa 20; Leber congenital amaurosis 2; not provided
- F70V (p.Phe70Val), rs1645945392, ClinGen CA340748974, ClinVar RCV003466254, ClinVar RCV004818348, REVEL 0.94, MetaLR 0.91, Conflicting interpretations, Leber congenital amaurosis 2; Retinal dystrophy; Leber congenital amaurosis
- D71G (p.Asp71Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F72S (p.Phe72Ser), rs1553153597, ClinGen CA340748948, ClinVar RCV000553292, ClinVar RCV002287424, REVEL 0.95, MetaLR 0.93, Conflicting interpretations, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- E74G (p.Glu74Gly), rs2100831191, ClinGen CA340748932, ClinVar RCV001936832, NCI-TCGA TCGA novel, MutPred 0.53, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- E74K (p.Glu74Lys), rs2100831197, ClinGen CA340748935, ClinVar RCV001957679, ClinVar RCV004816797, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- E74Q (p.Glu74Gln), rs2100831197, ClinGen CA340748934, ClinVar RCV001876355, Ensembl rs2100831197, MutPred 0.52, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- G75E (p.Gly75Glu), rs201062742, ClinGen CA902578, ClinVar RCV000326761, ClinVar RCV000381272, REVEL 0.88, MetaLR 0.96, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa; Retinitis pigmentosa 87 with
- G75R (p.Gly75Arg), rs267598701, ExAC rs267598701, gnomAD rs267598701, NCI-TCGA Cosmic COSV5201, REVEL 0.95, MetaLR 0.96, Variant assessed as somatic; moderate impact.
- H76P (p.His76Pro), rs1571172233, ClinGen CA340748920, ClinVar RCV001003188, Ensembl rs1571172233, Pathogenic, Leber congenital amaurosis
- H76R (p.His76Arg), rs1571172233, ClinGen CA340748921, ClinVar RCV001348498, Ensembl rs1571172233, MutPred 0.45, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- H76Y (p.His76Tyr), NCI-TCGA Cosmic COSV5201, Variant assessed as somatic; moderate impact.
- V77A (p.Val77Ala), Ensembl rs2100831151, REVEL 0.91, MetaLR 0.89, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- V77D (p.Val77Asp), NCI-TCGA Cosmic COSV5201, Variant assessed as somatic; moderate impact.
- Y79C (p.Tyr79Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in RP20
- Y79H (p.Tyr79His), rs61752869, ClinGen CA226528, ClinVar RCV000085182, ClinVar RCV003764790, REVEL 0.95, MetaLR 0.93, Likely pathogenic, RPE65-related recessive retinopathy
- R81I (p.Arg81Ile), rs1429137932, ClinGen CA340748885, ClinVar RCV000754977, ClinVar RCV001053470, REVEL 0.85, MetaLR 0.91, Pathogenic, RPE65-related recessive retinopathy
- F83L (p.Phe83Leu), rs2100828545, ClinGen CA340748617, ClinVar RCV001942144, Ensembl rs2100828545, MutPred 0.86, Pathogenic, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- F83S (p.Phe83Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I84M (p.Ile84Met), Ensembl rs1645931175, Likely benign
- I84T (p.Ile84Thr), Ensembl rs1571170742
- I84V (p.Ile84Val), TOPMed rs1261322768, gnomAD rs1261322768, REVEL 0.23, MetaLR 0.37, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- R85C (p.Arg85Cys), rs763317722, ClinGen CA902559, ClinVar RCV001098870, ClinVar RCV001098871, REVEL 0.82, MetaLR 0.92, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2; Retinitis pigmentosa
- R85H (p.Arg85His), rs61752870, ClinGen CA226529, ClinVar RCV000085183, ClinVar RCV002514526, REVEL 0.68, MetaLR 0.77, Uncertain significance, not specified; Leber congenital amaurosis 2; Retinitis pigmentosa 20
- R85L (p.Arg85Leu), ESP rs61752870, ExAC rs61752870, TOPMed rs61752870, gnomAD rs61752870, REVEL 0.78, MetaLR 0.81, Uncertain significance, in RP20
- R85S (p.Arg85Ser), ExAC rs763317722, TOPMed rs763317722, gnomAD rs763317722, Likely pathogenic, Retinitis pigmentosa 20
- T86A (p.Thr86Ala), rs2100828493, ClinGen CA340748555, ClinVar RCV001930328, Ensembl rs2100828493, MutPred 0.83, Uncertain significance, Leber congenital amaurosis
- T86I (p.Thr86Ile), NCI-TCGA Cosmic COSV9925, Variant assessed as somatic; moderate impact.
- T86N (p.Thr86Asn), rs1645931073, ClinGen CA340748547, ClinVar RCV001326816, ClinVar RCV001760420, REVEL 0.64, MetaLR 0.91, Uncertain significance, RPE65-related recessive retinopathy
- D87G (p.Asp87Gly), rs1645931040, ClinGen CA340748527, ClinVar RCV001923780, gnomAD rs1645931040, MutPred 0.79, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- D87V (p.Asp87Val), gnomAD rs1645931040, REVEL 0.91, MetaLR 0.93, Uncertain significance
- Y89F (p.Tyr89Phe), gnomAD rs1309759632, REVEL 0.67, MetaLR 0.84
- V90I (p.Val90Ile), rs370076628, ClinGen CA902553, ClinVar RCV001041393, ClinVar RCV001275288, REVEL 0.32, MetaLR 0.70, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20; not provided
- R91P (p.Arg91Pro), rs61752873, ClinGen CA226534, ClinVar RCV000085187, ClinVar RCV001250683, MutPred 0.90, Likely pathogenic, RPE65-related recessive retinopathy
- R91Q (p.Arg91Gln), rs61752873, ClinGen CA226533, ClinVar RCV000085186, ClinVar RCV001061074, REVEL 0.66, MetaLR 0.65, Pathogenic, RPE65-related recessive retinopathy
- R91W (p.Arg91Trp), rs61752871, ClinGen CA226531, ClinVar RCV000013994, ClinVar RCV000085184, REVEL 0.85, MetaLR 0.88, Pathogenic, RPE65-related recessive retinopathy
- A92S (p.Ala92Ser), ExAC rs778323735, gnomAD rs778323735, REVEL 0.56, MetaLR 0.69
- M93I (p.Met93Ile), TOPMed rs1645930731
- T94A (p.Thr94Ala), rs1645930710, ClinGen CA340748410, ClinVar RCV001350344, ClinVar RCV004691428, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2; not provided
- T94S (p.Thr94Ser), rs1645930710, ClinGen CA340748404, ClinVar RCV003803947, MutPred 0.38, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- E95G (p.Glu95Gly), rs2523445789, ClinGen CA340748386, ClinVar RCV003804757, Uncertain significance, Retinitis pigmentosa 20; Leber congenital amaurosis 2
- E95K (p.Glu95Lys), TOPMed rs61752874, Likely pathogenic, in RP20
- E95Q (p.Glu95Gln), rs61752874, ClinGen CA226535, NCI-TCGA Cosmic COSV5201, ClinVar RCV000085188, MutPred 0.69, Likely pathogenic, not provided
- I98T (p.Ile98Thr), rs1645930635, ClinGen CA340748334, ClinVar RCV001304231, ClinVar RCV001835468, MutPred 0.73, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- I98V (p.Ile98Val), rs2523445745, ClinGen CA340748339, ClinVar RCV002826330, Uncertain significance, Inborn genetic diseases
- V99I (p.Val99Ile), rs143056561, ClinGen CA902549, ClinVar RCV000972144, ClinVar RCV001097119, REVEL 0.52, MetaLR 0.73, Likely benign, RPE65-related recessive retinopathy
- I100K (p.Ile100Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I100L (p.Ile100Leu), rs142626873, ClinGen CA902548, ClinVar RCV001063520, ClinVar RCV001275334, REVEL 0.28, MetaLR 0.48, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- I100T (p.Ile100Thr), TOPMed rs1645930534, REVEL 0.83, MetaLR 0.84
- T101I (p.Thr101Ile), rs1444234037, ClinGen CA340748300, ClinVar RCV001073555, ClinVar RCV001089888, REVEL 0.88, MetaLR 0.88, Likely pathogenic, RPE65-related recessive retinopathy
- E102* (p.Glu102Ter), rs62642584, ClinGen CA226540, ClinVar RCV000085192, ClinVar RCV000763389, CADD 40.00, Pathogenic, in RP20 and LCA2
- E102K (p.Glu102Lys), rs62642584, ClinGen CA226539, ClinVar RCV000085191, ClinVar RCV005031580, MutPred 0.91, Likely pathogenic, Leber congenital amaurosis 2; Retinitis pigmentosa 20; Retinitis pigmentosa 87 w
- F103S (p.Phe103Ser), rs1645930469, ClinGen CA340748279, ClinVar RCV001246228, Ensembl rs1645930469, REVEL 0.97, MetaLR 0.92, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- G104D (p.Gly104Asp), rs61752875, ClinGen CA340748262, ClinVar RCV002634293, ClinVar RCV005425068, REVEL 0.96, MetaLR 0.94, Likely pathogenic, RPE65-related recessive retinopathy
- G104R (p.Gly104Arg), rs767478543, ClinGen CA340748268, ClinVar RCV001257819, ClinVar RCV005428156, MutPred 0.92, Likely pathogenic, RPE65-related recessive retinopathy
- G104S (p.Gly104Ser), rs767478543, ClinGen CA902547, ClinVar RCV002634294, ClinVar RCV003465996, REVEL 0.83, MetaLR 0.86, Pathogenic/Likely pathogenic, Leber congenital amaurosis; Leber congenital amaurosis 2; Retinitis pigmentosa 2
- G104V (p.Gly104Val), rs61752875, ClinGen CA226542, ClinVar RCV000085193, ClinVar RCV001588914, MutPred 0.91, Likely pathogenic, RPE65-related recessive retinopathy
- T105I (p.Thr105Ile), rs1260914084, ClinGen CA340748252, ClinVar RCV001591857, ClinVar RCV002569131, REVEL 0.94, MetaLR 0.94, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- T105N (p.Thr105Asn), rs1260914084, ClinGen CA340748250, ClinVar RCV001235816, ClinVar RCV001249891, MutPred 0.83, Uncertain significance, RPE65-related recessive retinopathy
- C106Y (p.Cys106Tyr), rs142052358, ClinGen CA902546, ClinVar RCV002918488, ClinVar RCV003883849, REVEL 0.20, MetaLR 0.37, Uncertain significance, Retinal dystrophy; Leber congenital amaurosis 2; Retinitis pigmentosa 20
- A107T (p.Ala107Thr), ExAC rs775867619, gnomAD rs775867619, REVEL 0.77, MetaLR 0.77
- A107V (p.Ala107Val), 1000Genomes rs202186372, ExAC rs202186372, gnomAD rs202186372, REVEL 0.88, MetaLR 0.86
- P109S (p.Pro109Ser), rs2523445525, ClinGen CA340748205, ClinVar RCV003792071, Uncertain significance, Leber congenital amaurosis 2; Retinitis pigmentosa 20
- D110G (p.Asp110Gly), rs1571170561, ClinGen CA340748193, ClinVar RCV000787882, ClinVar RCV002535759, REVEL 0.94, MetaLR 0.88, Pathogenic, RPE65-related recessive retinopathy
- P111H (p.Pro111His), rs2100828238, ClinGen CA340748180, ClinVar RCV001591852, Ensembl rs2100828238, MutPred 0.83, Uncertain significance, Leber congenital amaurosis 2
- P111S (p.Pro111Ser), rs886042220, ClinGen CA10603953, ClinVar RCV000288725, ClinVar RCV002519096, REVEL 0.91, MetaLR 0.93, Pathogenic, RPE65-related recessive retinopathy
- P111T (p.Pro111Thr), rs886042220, ClinGen CA340748185, ClinVar RCV001074561, ClinVar RCV003768999, MutPred 0.84, Likely pathogenic, RPE65-related recessive retinopathy
- C112* (p.Cys112Ter), rs1448061146, ClinGen CA340748160, ClinVar RCV003801208, gnomAD rs1448061146, CADD 38.00, Pathogenic
- C112Y (p.Cys112Tyr), ExAC rs759690120, gnomAD rs759690120, REVEL 0.92, MetaLR 0.93
- K113N (p.Lys113Asn), NCI-TCGA Cosmic COSV5201, Variant assessed as somatic; moderate impact.
- K113Q (p.Lys113Gln), ExAC rs776612353, TOPMed rs776612353, gnomAD rs776612353, REVEL 0.80, MetaLR 0.83
- I115M (p.Ile115Met), TOPMed rs1645929640, gnomAD rs1645929640, REVEL 0.84, MetaLR 0.89
- I115T (p.Ile115Thr), rs1645929674, ClinGen CA340748119, ClinVar RCV001377673, ClinVar RCV003469629, REVEL 0.94, MetaLR 0.91, Conflicting interpretations, Leber congenital amaurosis 2; Retinitis pigmentosa 20; not specified
- I115V (p.Ile115Val), TOPMed rs1051380960, gnomAD rs1051380960, REVEL 0.52, MetaLR 0.73
- F116L (p.Phe116Leu), TOPMed rs1315670304, gnomAD rs1315670304, REVEL 0.92, MetaLR 0.86
- S117F (p.Ser117Phe), rs2100828189, ClinGen CA340748086, ClinVar RCV001376366, Ensembl rs2100828189, MutPred 0.69, Uncertain significance, Retinitis pigmentosa 20
- S117Y (p.Ser117Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R118K (p.Arg118Lys), gnomAD rs1381010953, REVEL 0.83, MetaLR 0.84
- R118S (p.Arg118Ser), rs1015895028, ClinGen CA340748033, ClinVar RCV001089893, ClinVar RCV004595861, REVEL 0.87, MetaLR 0.83, Pathogenic, RPE65-related recessive retinopathy
- F119V (p.Phe119Val), Ensembl rs1571170394
- F120S (p.Phe120Ser), Ensembl rs1645928785
- F120V (p.Phe120Val), gnomAD rs1478850590, REVEL 0.73, MetaLR 0.72
Public RPE65 analysis runs
- RPE65 analysis run — RPE65 (1,062 variants) — completed 2026-08-18