REEP1 (Q9H902) variants and mutations
REEP1 (also known as Q9H902) is a human protein-coding gene encoding a receptor expression-enhancing protein 1 protein. It shapes tubular endoplasmic-reticulum membranes and supports interactions between the ER and neuronal cytoskeleton, particularly in long corticospinal axons. Pathogenic variants are a common cause of hereditary spastic paraplegia type 31 and can occasionally produce distal motor neuropathy. This analysis covers 348 REEP1 variants and mutations. Of these, 71% have computational variant effect predictions. Disease context includes Autosomal dominant spastic paraplegia type 31, hereditary spastic paraplegia 31, and neuronopathy, distal hereditary motor, type 5B. Example REEP1 variants include M1T, V2M, and W4G.
Variant analysis overview
- Gene: REEP1
- Protein: Q9H902
- UniProt accession: Q9H902
- Organism: Homo sapiens
- Variants analyzed: 348
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 295 unspecified-consequence records; 2 stop lost; 3 frameshift variants; 1 stop retained variant; 10 synonymous variants; 41 missense variants; 4 stop-gained variants
- Prediction scores: 247 variants have prediction scores (71% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Autosomal dominant spastic paraplegia type 31, hereditary spastic paraplegia 31, neuronopathy, distal hereditary motor, type 5B, hereditary spastic paraplegia, hereditary disease, spinal muscular atrophy, distal, autosomal recessive, 6, cardiomyopathy, Distal hereditary motor neuropathy type 5, Spastic paraplegia, atrial fibrillation, smoking initiation, alcohol drinking.
Protein structure and variant hotspots
- Protein features: 3 transmembrane segments; 1 post-translational modification sites.
- Structural context: 85 variants have structural context.
- PTM context: 1 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, MaveDB, LitVar.
Notable REEP1 variants
Examples include M1T, V2M, W4G, W4L, W4R, I6L, S7T, R8S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1T (p.Met1Thr), rs1681107508, ClinGen CA347725576, ClinVar RCV001210927, ClinVar RCV001268396, MetaLR 0.84, MetaSVM 0.76, Pathogenic/Likely pathogenic, Hereditary spastic paraplegia 31; Inborn genetic diseases; not provided
- V2M (p.Val2Met), rs898778508, ClinGen CA51490176, ClinVar RCV001929618, TOPMed rs898778508, CADD 21.30, PolyPhen-2 0.93, Uncertain significance, Hereditary spastic paraplegia 31
- W4G (p.Trp4Gly), rs863224189, ClinGen CA319904, ClinVar RCV000195547, ClinVar RCV000641687, MetaLR 0.55, MetaSVM -0.39, Uncertain significance, not provided; Inborn genetic diseases; Hereditary spastic paraplegia 31
- W4L (p.Trp4Leu), Ensembl rs867382999
- W4R (p.Trp4Arg), TOPMed rs863224189, gnomAD rs863224189, Uncertain significance
- I6L (p.Ile6Leu), rs1681106072, ClinGen CA347725514, ClinVar RCV001296769, ClinVar RCV006372455, AlphaMissense 0.09, MetaLR 0.56, Uncertain significance, Inborn genetic diseases; Hereditary spastic paraplegia 31
- S7T (p.Ser7Thr), Ensembl rs1681105904, CADD 22.00, PolyPhen-2 0.71
- R8S (p.Arg8Ser), NCI-TCGA TCGA novel, CADD 19.50, PolyPhen-2 0.20, Variant assessed as somatic; moderate impact.
- L9M (p.Leu9Met), TOPMed rs1681105721, gnomAD rs1681105721, CADD 21.10, PolyPhen-2 0.09
- I13M (p.Ile13Met), ExAC rs773346096, TOPMed rs773346096, gnomAD rs773346096, REVEL 0.75, CADD 22.70
- G15V (p.Gly15Val), rs2468983362, ClinGen CA347722751, ClinVar RCV003389301, REVEL 0.91, CADD 27.00, Likely pathogenic, Hereditary spastic paraplegia 31
- L17F (p.Leu17Phe), cosmic curated COSV10724
- L17I (p.Leu17Ile), rs1553465460, ClinGen CA347722733, NCI-TCGA Cosmic COSV9938, cosmic curated COSV99382, REVEL 0.72, CADD 26.00, Uncertain significance, Hereditary spastic paraplegia 31
- Y18C (p.Tyr18Cys), ESP rs144702296, ExAC rs144702296, TOPMed rs144702296
- Y18H (p.Tyr18His), cosmic curated COSV10957
- Y18N (p.Tyr18Asn), TOPMed rs1165498276, gnomAD rs1165498276, REVEL 0.90, CADD 28.80
- P19L (p.Pro19Leu), rs1060503496, ClinGen CA347722702, ClinVar RCV001391633, UniProt VAR 067265, AlphaMissense 1.00, MetaLR 0.98, Pathogenic/Likely pathogenic, Hereditary spastic paraplegia 31
- P19R (p.Pro19Arg), rs1060503496, ClinGen CA16611232, ClinVar RCV000466973, ClinVar RCV005421809, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, not provided; Hereditary spastic paraplegia 31
- P19T (p.Pro19Thr), rs2468983254, ClinGen CA347722707, ClinVar RCV003391646, ClinVar RCV005254785, REVEL 0.98, CADD 25.90, Conflicting interpretations, Hereditary spastic paraplegia 31; REEP1-related disorder
- A20E (p.Ala20Glu), rs121918262, ClinGen CA115247, ClinVar RCV000001939, ClinVar RCV000713454, REVEL 0.97, CADD 27.50, Pathogenic/Likely pathogenic, Inborn genetic diseases; not provided; Hereditary spastic paraplegia
- A20P (p.Ala20Pro), rs1266102026, ClinGen CA347722695, ClinVar RCV000516005, gnomAD rs1266102026, AlphaMissense 1.00, MetaLR 0.94, Likely pathogenic, Hereditary spastic paraplegia
- A20R (p.Ala20Arg), rs2468983226, ClinGen CA2580068279, ClinVar RCV002806831, Pathogenic, in SPG31
- A20T (p.Ala20Thr), rs1266102026, ClinGen CA347722697, ClinVar RCV001847504, ClinVar RCV003332349, REVEL 0.91, AlphaMissense 1.00, Conflicting interpretations, not provided; Hereditary spastic paraplegia; Hereditary spastic paraplegia 31
- A20V (p.Ala20Val), rs121918262, ClinGen CA347722689, cosmic curated COSV51256, ClinVar RCV001213470, REVEL 0.85, CADD 29.80, Likely pathogenic, Hereditary spastic paraplegia 31
- Y21C (p.Tyr21Cys), TOPMed rs1678134257
- Y22H (p.Tyr22His), Ensembl rs2104394911, REVEL 0.63, CADD 24.10
- S23F (p.Ser23Phe), NCI-TCGA Cosmic COSV5126, cosmic curated COSV51260, UniProt VAR 067266, Pathogenic, in SPG31
- S23P (p.Ser23Pro), rs2104394897, ClinGen CA347722644, ClinVar RCV001542525, Ensembl rs2104394897, REVEL 0.96, CADD 28.10, Likely pathogenic, Neuronopathy, distal hereditary motor, type 5B
- Y24* (p.Tyr24Ter), rs2468983090, ClinGen CA347722613, ClinVar RCV003498280, CADD 36.00, Pathogenic
- Y24C (p.Tyr24Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K25R (p.Lys25Arg), cosmic curated COSV51257
- A26T (p.Ala26Thr), rs1299952460, ClinGen CA347722583, ClinVar RCV000823273, ClinVar RCV002269321, REVEL 0.80, CADD 23.00, Uncertain significance, Hereditary spastic paraplegia 31; Inborn genetic diseases; not provided
- V27L (p.Val27Leu), NCI-TCGA Cosmic COSV9938, cosmic curated COSV99383, Variant assessed as somatic; moderate impact.
- V27M (p.Val27Met), ExAC rs775638750, gnomAD rs775638750, REVEL 0.85, CADD 27.20
- S29L (p.Ser29Leu), Ensembl rs867356107
- K30Q (p.Lys30Gln), rs1434743601, ClinGen CA347722516, ClinVar RCV001064773, TOPMed rs1434743601, REVEL 0.75, CADD 27.60, Uncertain significance, Hereditary spastic paraplegia 31
- D31N (p.Asp31Asn), cosmic curated COSV10455, REVEL 0.38, CADD 20.90
- I32F (p.Ile32Phe), rs745678615, ClinGen CA347722481, ClinVar RCV003862023, REVEL 0.54, CADD 24.00, Uncertain significance, Hereditary spastic paraplegia 31
- I32V (p.Ile32Val), rs745678615, ClinGen CA1748846, NCI-TCGA Cosmic COSV5125, cosmic curated COSV51257, REVEL 0.32, CADD 17.80, Uncertain significance, Hereditary spastic paraplegia 31
- K33N (p.Lys33Asn), rs2104394748, ClinGen CA347722453, ClinVar RCV001754644, Ensembl rs2104394748, AlphaMissense 0.99, MetaLR 0.72, Uncertain significance, not provided
- Y35N (p.Tyr35Asn), rs1574077431, ClinGen CA347722437, ClinVar RCV000790185, ClinVar RCV001352073, AlphaMissense 0.98, MetaLR 0.88, Uncertain significance, Hereditary spastic paraplegia 31
- Y35S (p.Tyr35Ser), rs2468982803, ClinGen CA347722432, ClinVar RCV002299280, Uncertain significance, Hereditary spastic paraplegia 31
- V36I (p.Val36Ile), ExAC rs765204754, gnomAD rs765204754, REVEL 0.59, CADD 25.20, Uncertain significance, Hereditary spastic paraplegia 31
- K37R (p.Lys37Arg), Ensembl rs1558898666
- W38* (p.Trp38Ter), rs1060503494, ClinGen CA16611230, ClinVar RCV000457155, ClinVar RCV001848818, Pathogenic
- M39I (p.Met39Ile), NCI-TCGA Cosmic COSV9938, cosmic curated COSV99383, Variant assessed as somatic; moderate impact.
- M39R (p.Met39Arg), rs1574052888, ClinGen CA347720137, ClinVar RCV000811126, ClinVar RCV000993057, AlphaMissense 1.00, MetaLR 0.91, Uncertain significance, Hereditary spastic paraplegia 31; not provided
- M40I (p.Met40Ile), TOPMed rs1677008442
- M40T (p.Met40Thr), TOPMed rs1677008769
- Y41* (p.Tyr41Ter), cosmic curated COSV51256
- Y41C (p.Tyr41Cys), rs2468890877, ClinGen CA347720105, ClinVar RCV003455905, Uncertain significance, Hereditary spastic paraplegia 31
- W42L (p.Trp42Leu), cosmic curated COSV10455
- W42R (p.Trp42Arg), rs2468890850, ClinGen CA347720098, ClinVar RCV002280598, ClinVar RCV002280599, REVEL 0.93, CADD 32.00, Pathogenic, Spinal muscular atrophy, distal, autosomal recessive, 6; Hereditary spastic para
- I43N (p.Ile43Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I44T (p.Ile44Thr), rs2468890818, ClinGen CA347720067, ClinVar RCV002294929, REVEL 0.80, CADD 24.00, Uncertain significance, Hereditary spastic paraplegia 31
- I44V (p.Ile44Val), ExAC rs759528213, gnomAD rs759528213, REVEL 0.37, CADD 17.30
- F45C (p.Phe45Cys), cosmic curated COSV10584
- F45L (p.Phe45Leu), gnomAD rs1387169886, Uncertain significance
- F45V (p.Phe45Val), rs1387169886, ClinGen CA347720059, ClinVar RCV001771307, gnomAD rs1387169886, AlphaMissense 1.00, MetaLR 0.83, Uncertain significance, not provided
- A46E (p.Ala46Glu), cosmic curated COSV10455
- A46P (p.Ala46Pro), cosmic curated COSV51256
- A46T (p.Ala46Thr), rs1558898635, ClinGen CA347720048, ClinVar RCV000713452, Ensembl rs1558898635, AlphaMissense 0.99, MetaLR 0.93, Uncertain significance, not provided
- A46V (p.Ala46Val), rs2468890749, ClinGen CA347720043, ClinVar RCV003498506, Uncertain significance, Hereditary spastic paraplegia 31
- T49A (p.Thr49Ala), TOPMed rs1433490355, REVEL 0.66, AlphaMissense 0.34, Uncertain significance
- T49I (p.Thr49Ile), NCI-TCGA Cosmic COSV9938, cosmic curated COSV99383, REVEL 0.65, CADD 22.60, Variant assessed as somatic; moderate impact.
- T49P (p.Thr49Pro), rs1433490355, ClinGen CA347720019, ClinVar RCV001391476, TOPMed rs1433490355, AlphaMissense 0.34, MetaLR 0.88, Uncertain significance, Spastic paraplegia
- T50A (p.Thr50Ala), NCI-TCGA Cosmic COSV9938, cosmic curated COSV99382, TOPMed rs1677006279, Variant assessed as somatic; moderate impact.
- T50I (p.Thr50Ile), rs886056410, ClinGen CA10616431, ClinVar RCV000294516, ClinVar RCV005268596, REVEL 0.61, CADD 23.70, Uncertain significance, Hereditary spastic paraplegia 31; Inborn genetic diseases
- E52D (p.Glu52Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E52K (p.Glu52Lys), rs2104303049, ClinGen CA347719990, ClinVar RCV001531493, Ensembl rs2104303049, AlphaMissense 1.00, MetaLR 0.96, Uncertain significance, not provided
- T53A (p.Thr53Ala), gnomAD rs1157781388, REVEL 0.43, CADD 23.60, Uncertain significance, Inborn genetic diseases
- F54V (p.Phe54Val), rs2468890474, ClinGen CA347719968, ClinVar RCV003148371, Uncertain significance, Neuronopathy, distal hereditary motor, type 5B
- T55K (p.Thr55Lys), rs1677004351, ClinGen CA347719949, ClinVar RCV001063448, ClinVar RCV002290992, REVEL 0.93, CADD 27.50, Uncertain significance, Hereditary spastic paraplegia 31
- D56H (p.Asp56His), rs1060503493, ClinGen CA347719942, ClinVar RCV001391637, Ensembl rs1060503493, AlphaMissense 1.00, MetaLR 0.92, Pathogenic, Hereditary spastic paraplegia 31
- D56N (p.Asp56Asn), rs1060503493, ClinGen CA16611113, ClinVar RCV000465053, ClinVar RCV005001063, AlphaMissense 1.00, MetaLR 0.92, Uncertain significance, Inborn genetic diseases; Neuronopathy, distal hereditary motor, type 5B; Heredit
- I57N (p.Ile57Asn), cosmic curated COSV10803
- F58I (p.Phe58Ile), cosmic curated COSV10724
- F58S (p.Phe58Ser), TOPMed rs1677004016
- L59H (p.Leu59His), rs1553462741, ClinGen CA347719903, ClinVar RCV003388204, AlphaMissense 0.98, MetaLR 0.90, Likely pathogenic, Hereditary spastic paraplegia 31
- L59P (p.Leu59Pro), rs1553462741, ClinGen CA347719901, ClinVar RCV000641685, Ensembl rs1553462741, REVEL 0.94, AlphaMissense 0.98, Uncertain significance, Hereditary spastic paraplegia 31
- C60Y (p.Cys60Tyr), rs2104302794, ClinGen CA347719895, ClinVar RCV001880480, Ensembl rs2104302794, AlphaMissense 0.63, MetaLR 0.70, Uncertain significance, Hereditary spastic paraplegia 31
- W61* (p.Trp61Ter), rs1558898568, ClinGen CA347719879, ClinVar RCV000760593, ClinVar RCV001855928, Pathogenic
- W61C (p.Trp61Cys), Ensembl rs1447806031
- W61R (p.Trp61Arg), gnomAD rs1248124433
- F62C (p.Phe62Cys), gnomAD rs1676464000, REVEL 0.94, CADD 29.90
- F62L (p.Phe62Leu), TOPMed rs1337560146, gnomAD rs1337560146, REVEL 0.35, CADD 23.60
- F64L (p.Phe64Leu), NCI-TCGA Cosmic COSV5125, cosmic curated COSV51255, Variant assessed as somatic; moderate impact.
- F64S (p.Phe64Ser), rs2468842582, ClinGen CA347717661, ClinVar RCV003191361, ClinVar RCV003497979, REVEL 0.95, CADD 32.00, Uncertain significance, Inborn genetic diseases; Hereditary spastic paraplegia 31
- Y65* (p.Tyr65Ter), rs1676463508, ClinGen CA347717637, ClinVar RCV001224005, ClinVar RCV004998744, Pathogenic
- Y65C (p.Tyr65Cys), rs1553461508, ClinGen CA347717642, ClinVar RCV000554008, ClinVar RCV001848943, AlphaMissense 0.99, MetaLR 0.97, Uncertain significance, Hereditary spastic paraplegia 31; Hereditary spastic paraplegia
- Y65H (p.Tyr65His), rs2104245077, ClinGen CA347717652, ClinVar RCV001847498, Ensembl rs2104245077, REVEL 0.97, CADD 29.50, Uncertain significance, Hereditary spastic paraplegia
- E67* (p.Glu67Ter), cosmic curated COSV99383
- E67V (p.Glu67Val), rs1553461506, ClinGen CA347717601, ClinVar RCV000641688, Ensembl rs1553461506, AlphaMissense 0.98, MetaLR 0.86, Uncertain significance, Hereditary spastic paraplegia 31
- L68P (p.Leu68Pro), rs2104244891, ClinGen CA347717585, ClinVar RCV001508449, ClinVar RCV001865942, AlphaMissense 1.00, MetaLR 0.92, Uncertain significance, not provided; Hereditary spastic paraplegia 31
- K69T (p.Lys69Thr), rs1676462791, ClinGen CA347717565, ClinVar RCV001331266, Ensembl rs1676462791, AlphaMissense 0.99, MetaLR 0.97, Uncertain significance, Neuronopathy, distal hereditary motor, type 5B
- I70R (p.Ile70Arg), rs1676462330, ClinGen CA347717543, ClinVar RCV001052430, Ensembl rs1676462330, AlphaMissense 1.00, MetaLR 0.92, Uncertain significance, Hereditary spastic paraplegia 31
- A71T (p.Ala71Thr), rs2468842391, ClinGen CA347717536, ClinVar RCV003601531, Uncertain significance, Hereditary spastic paraplegia 31
- A74S (p.Ala74Ser), rs1214003244, ClinGen CA347717468, ClinVar RCV003600602, TOPMed rs1214003244, REVEL 0.52, CADD 24.90, Uncertain significance, Hereditary spastic paraplegia 31
- W75* (p.Trp75Ter), rs2104244665, ClinGen CA347717453, ClinVar RCV001386988, Ensembl rs2104244665, Pathogenic
- W75G (p.Trp75Gly), TOPMed rs1676461294
- L77M (p.Leu77Met), cosmic curated COSV10803
- L77P (p.Leu77Pro), rs2468842275, ClinGen CA347717409, ClinVar RCV003100633, Uncertain significance, Hereditary spastic paraplegia 31
- P79S (p.Pro79Ser), cosmic curated COSV51258, Uncertain significance, Hereditary spastic paraplegia 31
- K82E (p.Lys82Glu), rs934249498, ClinGen CA51437056, ClinVar RCV001867667, TOPMed rs934249498, REVEL 0.78, CADD 26.20, Uncertain significance, Hereditary spastic paraplegia 31
- G83D (p.Gly83Asp), NCI-TCGA Cosmic COSV9938, cosmic curated COSV99382, Variant assessed as somatic; moderate impact.
- G83R (p.Gly83Arg), rs2104244562, ClinGen CA347717302, ClinVar RCV001730317, Ensembl rs2104244562, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, not provided
- G83V (p.Gly83Val), rs2468842177, ClinVar RCV004560465, ClinVar RCV005000522, Conflicting interpretations, not provided; Hereditary spastic paraplegia 31
- S84F (p.Ser84Phe), Ensembl rs1676459988
- S85N (p.Ser85Asn), ExAC rs770142567, gnomAD rs770142567, REVEL 0.73, CADD 25.60
- L87R (p.Leu87Arg), rs2104244362, ClinGen CA347717200, ClinVar RCV001391640, Ensembl rs2104244362, AlphaMissense 1.00, MetaLR 0.93, Pathogenic, Hereditary spastic paraplegia 31
- Y88* (p.Tyr88Ter), rs879254031, ClinGen CA10584227, ClinVar RCV000236987, Ensembl rs879254031, Likely pathogenic
- K90* (p.Lys90Ter), TOPMed rs1200576862
- K90R (p.Lys90Arg), rs1360820181, ClinGen CA347717148, ClinVar RCV002750786, ClinVar RCV003427500, AlphaMissense 0.90, MetaLR 0.83, Uncertain significance, not provided; Hereditary spastic paraplegia 31
- K90T (p.Lys90Thr), gnomAD rs1360820181
- V92E (p.Val92Glu), rs2468841912, ClinGen CA347717077, ClinVar RCV003223036, Uncertain significance, not provided
- V92I (p.Val92Ile), NCI-TCGA Cosmic COSV9938, cosmic curated COSV99382, Variant assessed as somatic; moderate impact.
- H93Y (p.His93Tyr), ExAC rs758589864, TOPMed rs758589864, gnomAD rs758589864, REVEL 0.88, CADD 26.90
- P94H (p.Pro94His), gnomAD rs1170051082, REVEL 0.95, CADD 27.60
- T95A (p.Thr95Ala), Ensembl rs2104244171, REVEL 0.39, CADD 21.80
- T95M (p.Thr95Met), cosmic curated COSV51256, Ensembl rs1553461480, REVEL 0.57, CADD 23.10
- L96P (p.Leu96Pro), rs1553461473, ClinGen CA347717002, ClinVar RCV000641684, ClinVar RCV003162889, AlphaMissense 1.00, MetaLR 0.91, Uncertain significance, Inborn genetic diseases; Hereditary spastic paraplegia 31
- S97A (p.Ser97Ala), rs1558891694, ClinGen CA347716991, ClinVar RCV001042224, gnomAD rs1558891694, AlphaMissense 0.16, MetaLR 0.54, Uncertain significance, Hereditary spastic paraplegia 31
- S97F (p.Ser97Phe), gnomAD rs1185128659, REVEL 0.80, CADD 31.00
- S97P (p.Ser97Pro), rs1558891694, ClinGen CA347716997, ClinVar RCV000701951, gnomAD rs1558891694, AlphaMissense 0.16, MetaLR 0.54, Uncertain significance, Hereditary spastic paraplegia 31
- S97T (p.Ser97Thr), gnomAD rs1558891694, REVEL 0.54, AlphaMissense 0.16, Uncertain significance, Inborn genetic diseases
- S98L (p.Ser98Leu), rs766247706, ClinGen CA1748788, ClinVar RCV001294796, ExAC rs766247706, REVEL 0.57, CADD 24.20, Uncertain significance, Hereditary spastic paraplegia 31
- K99E (p.Lys99Glu), rs2468841666, ClinGen CA347716957, ClinVar RCV002887779, Uncertain significance, Inborn genetic diseases
- E100K (p.Glu100Lys), rs2104243924, ClinGen CA347716943, ClinVar RCV002248153, ClinVar RCV003093994, AlphaMissense 1.00, MetaLR 0.87, Uncertain significance, not specified; Hereditary spastic paraplegia 31
- K101* (p.Lys101Ter), rs2104243903, ClinGen CA347716917, ClinVar RCV001730194, Ensembl rs2104243903, Pathogenic
- K101N (p.Lys101Asn), Ensembl rs1553461465
- E102K (p.Glu102Lys), rs2468827825, ClinGen CA347716599, ClinVar RCV003499253, REVEL 0.59, CADD 33.00, Uncertain significance, Hereditary spastic paraplegia 31
- C106F (p.Cys106Phe), NCI-TCGA Cosmic COSV9938, cosmic curated COSV99382, REVEL 0.33, CADD 22.80, Uncertain significance, Hereditary spastic paraplegia 31
- C106Y (p.Cys106Tyr), NCI-TCGA Cosmic COSV9938, Variant assessed as somatic; moderate impact.
- L107P (p.Leu107Pro), cosmic curated COSV51256, UniProt VAR 072611, Pathogenic, in SPG31
- L107V (p.Leu107Val), NCI-TCGA Cosmic COSV5125, cosmic curated COSV51259, Uncertain significance, Hereditary spastic paraplegia 31
- V108I (p.Val108Ile), rs1474498257, ClinGen CA347716453, cosmic curated COSV51258, ClinVar RCV000641686, REVEL 0.29, CADD 22.10, Uncertain significance, Hereditary spastic paraplegia 31
- V108A (p.Val108Ala), rs1454076238, gnomAD 2-86232650-A-G, CADD 11.60
- Q109* (p.Gln109Ter), NCI-TCGA Cosmic COSV5125, cosmic curated COSV51255, CADD 41.00, Variant assessed as somatic; high impact.
- Q109K (p.Gln109Lys), ExAC rs758454701, gnomAD rs758454701, REVEL 0.42, CADD 23.00
- Q109R (p.Gln109Arg), rs151242809, gnomAD 2-86232626-T-C, CADD 19.20
- A110E (p.Ala110Glu), rs1182977563, ClinGen CA347716398, ClinVar RCV001253597, gnomAD rs1182977563, AlphaMissense 0.99, MetaLR 0.83, Uncertain significance, Hereditary spastic paraplegia 31
- A110T (p.Ala110Thr), cosmic curated COSV10503
- A110V (p.Ala110Val), gnomAD rs1182977563, REVEL 0.54, AlphaMissense 0.99, Uncertain significance
- R113* (p.Arg113Ter), rs121918263, ClinGen CA115251, cosmic curated COSV51256, ClinVar RCV000001940, CADD 38.00, Pathogenic
- R113L (p.Arg113Leu), cosmic curated COSV51255
- R113Q (p.Arg113Gln), rs985433681, ClinGen CA51436082, cosmic curated COSV51255, NCI-TCGA Cosmic COSV5125, REVEL 0.35, CADD 22.80, Uncertain significance, Hereditary spastic paraplegia 31
- S114G (p.Ser114Gly), rs1249811179, ClinGen CA347716299, ClinVar RCV003602527, TOPMed rs1249811179, REVEL 0.34, CADD 21.90, Uncertain significance, Hereditary spastic paraplegia 31
- S114N (p.Ser114Asn), rs1676311757, ClinGen CA347716290, ClinVar RCV001043828, Ensembl rs1676311757, AlphaMissense 0.98, MetaLR 0.74, Uncertain significance, Hereditary spastic paraplegia 31
- Y115* (p.Tyr115Ter), rs138656911, ClinGen CA347716240, ClinVar RCV001047463, ClinVar RCV004720051, CADD 24.80, Pathogenic
- D116E (p.Asp116Glu), ESP rs377426129, REVEL 0.33, CADD 7.73
- D116H (p.Asp116His), ExAC rs201343132, TOPMed rs201343132, gnomAD rs201343132
- D116N (p.Asp116Asn), cosmic curated COSV51257, ExAC rs201343132, TOPMed rs201343132, gnomAD rs201343132, REVEL 0.33, CADD 23.00, Uncertain significance, Hereditary spastic paraplegia 31
- A117T (p.Ala117Thr), Ensembl rs1676310478
- A117V (p.Ala117Val), cosmic curated COSV51255
- L118P (p.Leu118Pro), rs1553461156, ClinGen CA347716184, ClinVar RCV001060595, TOPMed rs1553461156, REVEL 0.89, AlphaMissense 1.00, Uncertain significance, Hereditary spastic paraplegia 31
- L118R (p.Leu118Arg), rs1553461156, ClinGen CA347716180, ClinVar RCV000641691, TOPMed rs1553461156, AlphaMissense 1.00, MetaLR 0.76, Likely pathogenic, Hereditary spastic paraplegia 31
- V119A (p.Val119Ala), ESP rs373171938, ExAC rs373171938, TOPMed rs373171938, gnomAD rs373171938, REVEL 0.45, CADD 24.10
- V119L (p.Val119Leu), rs1676309660, ClinGen CA347716168, ClinVar RCV001214308, Ensembl rs1676309660, AlphaMissense 0.24, MetaLR 0.43, Uncertain significance, Hereditary spastic paraplegia 31
- H120R (p.His120Arg), gnomAD rs1232655129, REVEL 0.34, CADD 20.50
- F121L (p.Phe121Leu), rs1676308997, ClinGen CA347716111, ClinVar RCV003846363, gnomAD rs1676308997, REVEL 0.50, CADD 23.10, Uncertain significance, Hereditary spastic paraplegia 31
- F121Y (p.Phe121Tyr), ExAC rs750434521, gnomAD rs750434521, REVEL 0.34, CADD 22.50
- G122A (p.Gly122Ala), gnomAD rs1372179529, REVEL 0.74, CADD 25.20
- G122R (p.Gly122Arg), TOPMed rs1409832832, gnomAD rs1409832832, REVEL 0.85, CADD 26.80
- K123R (p.Lys123Arg), Ensembl rs1574035745, CADD 5.75
- R124L (p.Arg124Leu), cosmic curated COSV51257
- R124Q (p.Arg124Gln), rs757087677, ClinGen CA1748764, cosmic curated COSV51259, ClinVar RCV000701587, REVEL 0.36, CADD 22.50, Conflicting interpretations, Inborn genetic diseases; Hereditary spastic paraplegia 31
- R124W (p.Arg124Trp), cosmic curated COSV51259, gnomAD rs1296046852, REVEL 0.58, CADD 29.60
- G125D (p.Gly125Asp), TOPMed rs1676306767
- G125S (p.Gly125Ser), rs1375850288, ClinGen CA347716016, ClinVar RCV000686564, TOPMed rs1375850288, REVEL 0.65, CADD 24.30, Uncertain significance, Hereditary spastic paraplegia 31
- L126* (p.Leu126Ter), rs2468826608, ClinGen CA347716004, ClinVar RCV002468772, Likely pathogenic
- N127D (p.Asn127Asp), rs1676306574, ClinGen CA347715989, ClinVar RCV001139904, Ensembl rs1676306574, AlphaMissense 0.76, MetaLR 0.65, Uncertain significance, Hereditary spastic paraplegia 31
- N127T (p.Asn127Thr), Ensembl rs1574035711
- V128G (p.Val128Gly), ExAC rs762454693, gnomAD rs762454693
- V128L (p.Val128Leu), ExAC rs763762442, gnomAD rs763762442
- V128M (p.Val128Met), ExAC rs763762442, gnomAD rs763762442, REVEL 0.36, CADD 22.40
- A129P (p.Ala129Pro), ExAC rs764856171, gnomAD rs764856171
- A130T (p.Ala130Thr), rs777316624, ClinGen CA1748757, NCI-TCGA Cosmic COSV5125, cosmic curated COSV51256, REVEL 0.41, CADD 22.80, Uncertain significance, Hereditary spastic paraplegia 31
- T131A (p.Thr131Ala), rs1558889637, ClinGen CA347715894, ClinVar RCV000698241, TOPMed rs1558889637, REVEL 0.33, CADD 23.60, Uncertain significance, Hereditary spastic paraplegia 31
- T131I (p.Thr131Ile), rs1553461131, ClinGen CA347715883, ClinVar RCV000641682, Ensembl rs1553461131, AlphaMissense 0.93, MetaLR 0.64, Uncertain significance, Hereditary spastic paraplegia 31
- A132V (p.Ala132Val), rs1235877574, ClinGen CA347715866, cosmic curated COSV10803, ClinVar RCV003601975, REVEL 0.53, CADD 23.20, Uncertain significance, Hereditary spastic paraplegia 31
Public REEP1 analysis runs
- REEP1 analysis run — REEP1 (348 variants) — completed 2026-08-22