GCH1 (GTP cyclohydrolase 1) variants and mutations
GCH1 (also known as GTP cyclohydrolase 1) is a human protein-coding gene encoding a GTP cyclohydrolase 1 protein. It catalyzes the rate-limiting step in tetrahydrobiopterin synthesis, supplying an essential cofactor for dopamine, serotonin, norepinephrine, and nitric-oxide production. Dominant loss-of-function variants classically cause dopa-responsive dystonia, while biallelic deficiency can produce severe neurotransmitter disease. This analysis covers 552 GCH1 variants and mutations. Of these, 94% have computational variant effect predictions. Disease context includes dystonia 5, GTP cyclohydrolase I deficiency with hyperphenylalaninemia, and Hyperphenylalaninemia. Example GCH1 variants include M1I, M1L, and M1V.
Variant analysis overview
- Gene: GCH1
- Protein: GTP cyclohydrolase 1
- UniProt accession: P30793
- Organism: Homo sapiens
- Variants analyzed: 552
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 397 unspecified-consequence records; 6 stop lost; 2 stop retained variant; 6 frameshift variants; 48 synonymous variants; 87 missense variants; 8 stop-gained variants; 1 in-frame deletions; 4 splice-region variants; 1 in-frame insertions; 4 substitution
- Prediction scores: 521 variants have prediction scores (94% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: dystonia 5, GTP cyclohydrolase I deficiency with hyperphenylalaninemia, Hyperphenylalaninemia, GTP cyclohydrolase I deficiency, Dystonia, Spastic paraplegia, Autosomal recessive dopa-responsive dystonia, dystonic disorder, hereditary disease, dopa-responsive dystonia, Intellectual disability, Parkinson disease.
Protein structure and variant hotspots
- Protein features: 3 binding sites; 2 post-translational modification sites.
- PTM context: 4 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, ClinGen, MaveDB, LitVar.
Notable GCH1 variants
Examples include M1I, M1L, M1V, M1T, E2K, G4D, G4R, G4S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs104894439, ClinGen CA254721, ClinVar RCV000009859, MetaLR 0.95, MetaSVM 1.20, Pathogenic, Dystonia 5
- M1L (p.Met1Leu), rs1555362907, ClinGen CA389795046, ClinVar RCV001388236, ClinGen CA389795057, MetaLR 0.94, MetaSVM 0.95, Pathogenic, Dystonia 5; GTP cyclohydrolase I deficiency
- M1V (p.Met1Val), rs1555362907, ClinGen CA389795049, ClinVar RCV000796195, ClinVar RCV002245673, MetaLR 0.94, MetaSVM 0.95, Pathogenic, not provided; Dystonia 5; GTP cyclohydrolase I deficiency
- M1T (p.Met1Thr), rs917108513, []
- E2K (p.Glu2Lys), rs2140127817, ClinGen CA389795019, ClinVar RCV002262440, Ensembl rs2140127817, AlphaMissense 0.23, MetaLR 0.96, Uncertain significance, not provided
- G4D (p.Gly4Asp), rs2140127797, ClinGen CA389794965, ClinVar RCV001806483, ClinVar RCV003772219, REVEL 0.43, CADD 22.70, Uncertain significance, not provided; Dystonia 5; GTP cyclohydrolase I deficiency
- G4R (p.Gly4Arg), ExAC rs764013857, TOPMed rs764013857, gnomAD rs764013857, REVEL 0.47, CADD 20.90, Uncertain significance
- G4S (p.Gly4Ser), rs764013857, ClinGen CA389794973, ClinVar RCV003131003, ClinVar RCV003778702, REVEL 0.47, CADD 22.80, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency; not provided
- P5A (p.Pro5Ala), rs2040587976, ClinGen CA389794942, ClinVar RCV001208688, Ensembl rs2040587976, REVEL 0.31, CADD 21.30, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- V6E (p.Val6Glu), gnomAD rs1206396500, REVEL 0.31, CADD 22.50
- V6L (p.Val6Leu), rs1413964407, TOPMed rs1413964407, ClinGen CA389794927, ClinVar RCV001948499, REVEL 0.32, CADD 16.10, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5; GTP cyclohydrolase I deficiency wit
- R7G (p.Arg7Gly), gnomAD rs1167936240, REVEL 0.30, CADD 18.40, Uncertain significance
- R7L (p.Arg7Leu), TOPMed rs1170513883, gnomAD rs1170513883, REVEL 0.33, CADD 16.20
- R7P (p.Arg7Pro), TOPMed rs1170513883, gnomAD rs1170513883, REVEL 0.32, CADD 15.90
- R7W (p.Arg7Trp), rs1167936240, ClinGen CA389794903, ClinVar RCV003233173, gnomAD rs1167936240, REVEL 0.33, CADD 22.90, Uncertain significance, not provided
- A8P (p.Ala8Pro), rs529381971, ClinGen CA389794892, ClinVar RCV001956897, 1000Genomes rs529381971, REVEL 0.35, CADD 14.30, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- A8S (p.Ala8Ser), rs529381971, ClinGen CA260531806, ClinVar RCV001241278, 1000Genomes rs529381971, REVEL 0.38, CADD 12.60, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- A8T (p.Ala8Thr), rs529381971, ClinGen CA260531807, ClinVar RCV000711751, ClinVar RCV001055986, REVEL 0.27, CADD 13.20, Uncertain significance, not provided; Inborn genetic diseases; GTP cyclohydrolase I deficiency
- P9L (p.Pro9Leu), TOPMed rs1262075886, gnomAD rs1262075886, REVEL 0.24, CADD 12.60
- P9S (p.Pro9Ser), rs1248808303, ClinGen CA389794875, ClinVar RCV003798085, TOPMed rs1248808303, REVEL 0.24, CADD 8.73, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- A10S (p.Ala10Ser), TOPMed rs946737110, REVEL 0.28, CADD 11.10
- E11A (p.Glu11Ala), gnomAD rs1272621459, REVEL 0.45, CADD 18.10
- E11D (p.Glu11Asp), 1000Genomes rs2140127730, REVEL 0.41, CADD 13.40, Likely benign
- P13A (p.Pro13Ala), TOPMed rs2040587282
- P13L (p.Pro13Leu), gnomAD rs2040587239, REVEL 0.35, CADD 21.10
- R14W (p.Arg14Trp), gnomAD rs1487411316, REVEL 0.45, CADD 23.50
- G15D (p.Gly15Asp), gnomAD rs2040587010, UniProt VAR 002632, REVEL 0.35, CADD 12.30, Uncertain significance, in HGCH-3
- G15S (p.Gly15Ser), rs1214036983, ClinGen CA389794762, ClinVar RCV003060157, TOPMed rs1214036983, REVEL 0.28, CADD 10.30, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- A16T (p.Ala16Thr), Ensembl rs1156577725, REVEL 0.43, CADD 10.80
- C18G (p.Cys18Gly), TOPMed rs1299121897, gnomAD rs1299121897, SIFT 0.03
- C18S (p.Cys18Ser), TOPMed rs1299121897, gnomAD rs1299121897, REVEL 0.52, CADD 22.80
- C18Y (p.Cys18Tyr), TOPMed rs2040586875, REVEL 0.51, CADD 23.60, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- S19I (p.Ser19Ile), gnomAD rs1457270763, REVEL 0.41, CADD 18.90
- N20S (p.Asn20Ser), rs2040586742, ClinGen CA389794636, ClinVar RCV001556174, ClinVar RCV002568357, REVEL 0.47, CADD 22.70, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5; not provided
- G21W (p.Gly21Trp), TOPMed rs1342263570, REVEL 0.56, CADD 24.00, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- F22V (p.Phe22Val), gnomAD rs1220614834, REVEL 0.35, CADD 20.40
- P23A (p.Pro23Ala), gnomAD rs1308135163, REVEL 0.40, CADD 11.50
- P23L (p.Pro23Leu), rs41298432, ClinGen CA7193683, cosmic curated COSV54302, ClinVar RCV000263675, REVEL 0.61, CADD 15.90, Conflicting interpretations, GTP cyclohydrolase I deficiency; Dystonia 5; not provided
- E24* (p.Glu24Ter), TOPMed rs1444127928, CADD 36.00
- E24D (p.Glu24Asp), TOPMed rs1206554765, gnomAD rs1206554765, REVEL 0.24, CADD 11.80, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- E24K (p.Glu24Lys), cosmic curated COSV10878, REVEL 0.29, CADD 18.90
- R25W (p.Arg25Trp), rs2040586271, ClinGen CA389794534, ClinVar RCV002611010, TOPMed rs2040586271, REVEL 0.32, CADD 22.50, Uncertain significance, Inborn genetic diseases; GTP cyclohydrolase I deficiency; Dystonia 5
- P28A (p.Pro28Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P28L (p.Pro28Leu), rs774568081, ClinGen CA7193680, ClinVar RCV001949710, ClinVar RCV006280820, REVEL 0.38, CADD 17.10, Uncertain significance, not provided; GTP cyclohydrolase I deficiency; Dystonia 5
- P28S (p.Pro28Ser), rs759709001, ClinGen CA7193681, ClinVar RCV003011708, ExAC rs759709001, REVEL 0.34, CADD 8.39, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- P30R (p.Pro30Arg), rs1477733062, ClinGen CA389794441, ClinVar RCV001904708, TOPMed rs1477733062, REVEL 0.34, CADD 17.10, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- P30S (p.Pro30Ser), TOPMed rs944665606, gnomAD rs944665606, REVEL 0.37, CADD 14.10, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- G31E (p.Gly31Glu), TOPMed rs1463121244, gnomAD rs1463121244, REVEL 0.33, CADD 15.70, Uncertain significance
- G31R (p.Gly31Arg), rs2040585757, ClinGen CA389794433, ClinVar RCV003792396, Ensembl rs2040585757, REVEL 0.34, CADD 18.70, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- G31V (p.Gly31Val), rs1463121244, ClinGen CA389794416, ClinVar RCV003957025, TOPMed rs1463121244, REVEL 0.31, CADD 16.40, Uncertain significance, GCH1-related disorder
- P32S (p.Pro32Ser), TOPMed rs1456164846, REVEL 0.36, CADD 15.60
- S33C (p.Ser33Cys), rs1373130817, ClinGen CA389794395, ClinVar RCV002016150, gnomAD rs1373130817, REVEL 0.35, CADD 22.30, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- S33G (p.Ser33Gly), gnomAD rs1373130817, REVEL 0.22, CADD 18.20, Uncertain significance
- S33R (p.Ser33Arg), TOPMed rs1320254777, gnomAD rs1320254777, REVEL 0.23, CADD 16.10
- R34S (p.Arg34Ser), Ensembl rs954444362, REVEL 0.40, CADD 14.70
- A36E (p.Ala36Glu), gnomAD rs1431116951, REVEL 0.35, CADD 13.70
- A36S (p.Ala36Ser), gnomAD rs1030068813, REVEL 0.19, CADD 14.40
- A36V (p.Ala36Val), gnomAD rs1431116951, REVEL 0.28, CADD 15.20, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- E37* (p.Glu37Ter), rs2140127551, ClinGen CA389794330, ClinVar RCV001866517, Ensembl rs2140127551, Pathogenic
- E37G (p.Glu37Gly), gnomAD rs1281740862, REVEL 0.29, CADD 22.00
- P39S (p.Pro39Ser), ExAC rs770932357, gnomAD rs770932357, REVEL 0.29, CADD 0.34, Uncertain significance
- P39T (p.Pro39Thr), rs770932357, ClinGen CA389794291, ClinVar RCV002030849, ExAC rs770932357, REVEL 0.28, CADD 0.31, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- P40L (p.Pro40Leu), TOPMed rs995999325, gnomAD rs995999325, REVEL 0.32, CADD 19.40, Uncertain significance
- P40R (p.Pro40Arg), rs995999325, ClinGen CA260531777, ClinVar RCV000556657, ClinVar RCV002527705, REVEL 0.36, CADD 18.70, Uncertain significance, Inborn genetic diseases; Dystonia 5; GTP cyclohydrolase I deficiency
- P40S (p.Pro40Ser), TOPMed rs2040585105, REVEL 0.33, CADD 20.10
- P42L (p.Pro42Leu), gnomAD rs1481021061, REVEL 0.38, CADD 19.30
- P42S (p.Pro42Ser), gnomAD rs1197458063, REVEL 0.37, CADD 20.20
- E43* (p.Glu43Ter), gnomAD rs1255523585, CADD 36.00
- E43K (p.Glu43Lys), gnomAD rs1255523585, REVEL 0.41, CADD 19.60
- A44T (p.Ala44Thr), gnomAD rs1208054607, REVEL 0.24, CADD 15.00
- A44V (p.Ala44Val), TOPMed rs2040584625, SIFT 0.27, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- S46G (p.Ser46Gly), ExAC rs773925613, TOPMed rs773925613, gnomAD rs773925613, REVEL 0.31, CADD 12.70
- S46N (p.Ser46Asn), rs2504540653, ClinGen CA389794201, ClinVar RCV003030377, REVEL 0.31, CADD 14.60, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- S46R (p.Ser46Arg), rs1239964950, ClinGen CA389794197, ClinVar RCV003804876, ClinVar RCV004818418, REVEL 0.38, CADD 17.20, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- A47E (p.Ala47Glu), rs2040584415, ClinGen CA389794188, ClinVar RCV001966392, TOPMed rs2040584415, REVEL 0.28, CADD 16.30, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- A47V (p.Ala47Val), rs2040584415, ClinGen CA389794190, ClinVar RCV003788930, TOPMed rs2040584415, REVEL 0.26, CADD 16.60, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- Q48* (p.Gln48Ter), rs104894444, ClinGen CA254727, ClinVar RCV000009871, ClinVar RCV001390287, CADD 36.00, Pathogenic
- Q48K (p.Gln48Lys), TOPMed rs104894444, Uncertain significance, Inborn genetic diseases
- P49A (p.Pro49Ala), rs573085618, ClinGen CA7193676, ClinVar RCV002093995, 1000Genomes rs573085618, REVEL 0.29, CADD 14.30, Likely benign, GTP cyclohydrolase I deficiency; Dystonia 5
- P49L (p.Pro49Leu), gnomAD rs1330315044, SIFT 0.37, Uncertain significance, Inborn genetic diseases
- P49S (p.Pro49Ser), rs573085618, ClinGen CA7193675, ClinVar RCV003783778, 1000Genomes rs573085618, REVEL 0.34, CADD 15.60, Uncertain significance, not provided
- D51E (p.Asp51Glu), rs745516526, ClinGen CA16606999, ClinVar RCV000424438, ClinVar RCV002522692, REVEL 0.33, CADD 20.90, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency; not provided
- D51Y (p.Asp51Tyr), ExAC rs755299126, gnomAD rs755299126, REVEL 0.49, CADD 24.80
- G52C (p.Gly52Cys), rs375788167, ClinGen CA389794139, ClinVar RCV003786507, ESP rs375788167, REVEL 0.36, CADD 24.70, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- G52S (p.Gly52Ser), rs375788167, ClinGen CA7193671, ClinVar RCV003081851, ESP rs375788167, REVEL 0.27, CADD 20.20, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- W53* (p.Trp53Ter), rs2140127425, ClinGen CA389794128, ClinVar RCV001382935, Ensembl rs2140127425, CADD 41.00, Pathogenic
- W53C (p.Trp53Cys), NCI-TCGA Cosmic COSV9958, cosmic curated COSV99582, REVEL 0.58, CADD 24.00, Variant assessed as somatic; moderate impact.
- W53X, rs886041708, Pathogenic
- G55D (p.Gly55Asp), rs1464045587, ClinGen CA389794102, ClinVar RCV003785014, TOPMed rs1464045587, REVEL 0.24, CADD 15.00, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- G55S (p.Gly55Ser), rs2140127419, ClinGen CA389794106, ClinVar RCV001895867, Ensembl rs2140127419, AlphaMissense 0.09, MetaLR 0.93, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- G55V (p.Gly55Val), TOPMed rs1464045587, gnomAD rs1464045587, SIFT 0.10, Uncertain significance
- E56G (p.Glu56Gly), gnomAD rs1376965947, SIFT 0.04
- E56K (p.Glu56Lys), NCI-TCGA Cosmic COSV5430, cosmic curated COSV54301, REVEL 0.52, CADD 22.70, Variant assessed as somatic; moderate impact.
- R57L (p.Arg57Leu), cosmic curated COSV99582, SIFT 0.04
- R57Q (p.Arg57Gln), rs756782285, ClinGen CA7193670, ClinVar RCV002882312, ExAC rs756782285, REVEL 0.47, CADD 22.70, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- R57W (p.Arg57Trp), cosmic curated COSV54301, REVEL 0.58, CADD 25.90
- P58L (p.Pro58Leu), gnomAD rs1438904628, REVEL 0.38, CADD 24.80
- P58S (p.Pro58Ser), rs2040583643, ClinGen CA389794075, ClinVar RCV002044044, TOPMed rs2040583643, REVEL 0.37, CADD 22.60, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- R59C (p.Arg59Cys), ExAC rs753312849, TOPMed rs753312849, gnomAD rs753312849, REVEL 0.60, CADD 25.90, Uncertain significance
- R59G (p.Arg59Gly), rs753312849, ClinGen CA7193669, ClinVar RCV002949635, ExAC rs753312849, REVEL 0.63, CADD 25.00, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- S60G (p.Ser60Gly), TOPMed rs2040583421, REVEL 0.50, CADD 22.20
- S60R (p.Ser60Arg), TOPMed rs2040583421, REVEL 0.58, CADD 22.50
- S60T (p.Ser60Thr), ExAC rs756067922, gnomAD rs756067922, REVEL 0.55, CADD 21.00
- E62D (p.Glu62Asp), rs752590798, ClinGen CA7193666, ClinVar RCV001905646, ExAC rs752590798, AlphaMissense 0.16, MetaLR 0.95, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- E62G (p.Glu62Gly), gnomAD rs1162192311, REVEL 0.50, CADD 24.70
- D63N (p.Asp63Asn), rs1404198001, ClinGen CA389794019, ClinVar RCV003812692, gnomAD rs1404198001, REVEL 0.46, CADD 23.50, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- N64D (p.Asn64Asp), TOPMed rs2040583041, SIFT 0.07
- E65Q (p.Glu65Gln), rs1281386674, ClinGen CA389793992, ClinVar RCV001908001, ClinVar RCV004980831, REVEL 0.31, CADD 22.20, Uncertain significance, Inborn genetic diseases; Dystonia 5; GTP cyclohydrolase I deficiency
- E65V (p.Glu65Val), rs2140127337, ClinGen CA389793987, ClinVar RCV001953305, Ensembl rs2140127337, REVEL 0.50, CADD 23.50, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- L66P (p.Leu66Pro), rs1042390728, ClinGen CA260531758, cosmic curated COSV54304, ClinVar RCV001945631, REVEL 0.56, CADD 23.60, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- N67K (p.Asn67Lys), Ensembl rs2040582634, SIFT 0.18, Uncertain significance, not provided
- N67T (p.Asn67Thr), gnomAD rs1240134623, REVEL 0.41, CADD 22.50
- L68F (p.Leu68Phe), rs2040582582, ClinGen CA389793956, ClinVar RCV002790253, ClinVar RCV006281070, REVEL 0.59, CADD 26.80, Uncertain significance, not provided; Dystonia 5; GTP cyclohydrolase I deficiency
- P69L (p.Pro69Leu), rs56127440, ClinGen CA211433, ClinVar RCV000148505, ClinVar RCV000265088, REVEL 0.82, CADD 26.00, Conflicting interpretations, GTP cyclohydrolase I deficiency; Dystonia 5; not provided
- P69R (p.Pro69Arg), 1000Genomes rs56127440, ESP rs56127440, ExAC rs56127440, TOPMed rs56127440, REVEL 0.68, CADD 24.00, Benign
- N70K (p.Asn70Lys), ExAC rs763168809, TOPMed rs763168809, gnomAD rs763168809, REVEL 0.37, CADD 15.10
- N70Y (p.Asn70Tyr), gnomAD rs1356789844, REVEL 0.33, CADD 22.60
- L71P (p.Leu71Pro), rs1555362843, ClinGen CA389793926, ClinVar RCV000806490, Ensembl rs1555362843, AlphaMissense 0.99, MetaLR 0.99, Likely pathogenic, GTP cyclohydrolase I deficiency; Dystonia 5
- L71Q (p.Leu71Gln), UniProt VAR 016888, SIFT 0.00, Pathogenic, in DRD
- A72G (p.Ala72Gly), rs2504539859, ClinGen CA389793914, ClinVar RCV002795250, REVEL 0.56, CADD 23.40, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- A72P (p.Ala72Pro), gnomAD rs1160103349, REVEL 0.68, CADD 28.10
- A72V (p.Ala72Val), cosmic curated COSV54302, SIFT 0.11
- A73V (p.Ala73Val), rs2140127256, ClinGen CA389793902, ClinVar RCV002247857, Ensembl rs2140127256, AlphaMissense 0.14, MetaLR 0.96, Uncertain significance, not specified
- A74V (p.Ala74Val), UniProt VAR 016889, SIFT 0.01, Pathogenic, in DRD
- Y75C (p.Tyr75Cys), UniProt VAR 072733, SIFT 0.01, Uncertain significance
- S77C (p.Ser77Cys), rs748666093, ClinGen CA7193659, ClinVar RCV000699697, ExAC rs748666093, REVEL 0.55, CADD 24.90, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- I78M (p.Ile78Met), rs747393714, ClinGen CA7193657, ClinVar RCV000995178, ExAC rs747393714, REVEL 0.77, CADD 22.70, Uncertain significance, not provided
- I78N (p.Ile78Asn), ExAC rs777135030, TOPMed rs777135030, gnomAD rs777135030, REVEL 0.93, CADD 32.00
- L79P (p.Leu79Pro), UniProt VAR 002634, REVEL 0.97, CADD 32.00, Pathogenic, in DRD
- S80C (p.Ser80Cys), rs2140127221, ClinGen CA389793834, ClinVar RCV001997935, ClinVar RCV006367874, AlphaMissense 0.05, MetaLR 0.96, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5; Inborn genetic diseases
- S80N (p.Ser80Asn), rs770547722, ClinGen CA7193654, ClinVar RCV001546383, ClinVar RCV002568967, REVEL 0.39, CADD 21.70, Conflicting interpretations, not specified; not provided; GTP cyclohydrolase I deficiency
- S80R (p.Ser80Arg), ExAC rs748890014, gnomAD rs748890014, REVEL 0.30, CADD 19.30
- S81P (p.Ser81Pro), rs2140127208, ClinGen CA389793826, ClinVar RCV001960944, Ensembl rs2140127208, AlphaMissense 0.98, MetaLR 0.97, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- L82P (p.Leu82Pro), cosmic curated COSV10583
- G83A (p.Gly83Ala), UniProt VAR 016890, REVEL 0.90, CADD 26.40, Pathogenic, in DRD
- E84* (p.Glu84Ter), rs755556239, ClinGen CA389793795, ClinVar RCV001231564, ClinVar RCV002250735, AlphaMissense 0.96, MetaLR 0.99, Pathogenic
- E84D (p.Glu84Asp), TOPMed rs1263510185, gnomAD rs1263510185, REVEL 0.43, CADD 23.00, Likely benign
- E84G (p.Glu84Gly), rs1595031209, ClinGen CA389793793, ClinVar RCV000793795, Ensembl rs1595031209, AlphaMissense 0.97, MetaLR 0.99, Likely pathogenic, Dystonia 5; GTP cyclohydrolase I deficiency
- E84Q (p.Glu84Gln), rs755556239, ClinGen CA7193651, ClinVar RCV001338249, ExAC rs755556239, REVEL 0.63, AlphaMissense 0.96, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- N85K (p.Asn85Lys), ExAC rs752645828, gnomAD rs752645828, SIFT 1.00, Likely benign
- P86L (p.Pro86Leu), cosmic curated COSV54301
- P86R (p.Pro86Arg), rs1555362836, ClinGen CA389793764, ClinVar RCV000634831, Ensembl rs1555362836, AlphaMissense 0.62, MetaLR 0.99, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- P86S (p.Pro86Ser), ExAC rs781177989, gnomAD rs781177989, REVEL 0.77, CADD 27.10
- P86T (p.Pro86Thr), ExAC rs781177989, gnomAD rs781177989, REVEL 0.54, CADD 23.10
- Q87H (p.Gln87His), rs2504539417, ClinGen CA389793748, ClinVar RCV002816553, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- Q87P (p.Gln87Pro), rs1595031190, ClinGen CA389793753, ClinVar RCV000992032, ClinVar RCV001858745, AlphaMissense 0.58, MetaLR 0.96, Uncertain significance, not provided; GTP cyclohydrolase I deficiency; Dystonia 5
- Q87S (p.Gln87Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R88G (p.Arg88Gly), ExAC rs104894433, gnomAD rs104894433, REVEL 0.92, AlphaMissense 0.98, Likely pathogenic, Dystonia 5
- R88L (p.Arg88Leu), rs2140127157, ClinGen CA389793742, ClinVar RCV001814484, ClinVar RCV002071935, AlphaMissense 0.99, MetaLR 0.99, Likely pathogenic, Abnormal central motor function; not provided
- R88P (p.Arg88Pro), UniProt VAR 002635, REVEL 0.97, CADD 32.00, Pathogenic, in DRD
- R88W (p.Arg88Trp), rs104894433, ClinGen CA254718, ClinVar RCV000009853, UniProt VAR 002636, AlphaMissense 0.98, MetaLR 0.99, Pathogenic, Dystonia 5
- Q89K (p.Gln89Lys), gnomAD rs1293402606, REVEL 0.64, CADD 24.30
- Q89R (p.Gln89Arg), rs2140127145, ClinGen CA389793737, ClinVar RCV001896308, Ensembl rs2140127145, AlphaMissense 0.38, MetaLR 0.98, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- G90R (p.Gly90Arg), rs2504539350, ClinGen CA389793728, ClinVar RCV003803287, ClinVar RCV005620489, Conflicting interpretations, GTP cyclohydrolase I deficiency; Dystonia 5; not provided
- G90V (p.Gly90Val), UniProt VAR 016892, SIFT 0.00, Pathogenic, in DRD
- L91Q (p.Leu91Gln), rs2504539343, ClinGen CA389793715, ClinVar RCV003027954, Likely pathogenic, GTP cyclohydrolase I deficiency; Dystonia 5
- L92F (p.Leu92Phe), rs763294577, ClinGen CA389793710, ClinVar RCV001329662, ClinVar RCV005225374, AlphaMissense 0.53, MetaLR 0.98, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- L92I (p.Leu92Ile), rs763294577, ClinGen CA7193645, ClinVar RCV000626091, ClinVar RCV005213365, REVEL 0.47, AlphaMissense 0.53, Conflicting interpretations, 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency; Dystonia 5; GTP cyclohydrola
- L92P (p.Leu92Pro), rs2504539308, ClinGen CA389793709, ClinVar RCV003142379, Uncertain significance, Dystonia 5
- K93N (p.Lys93Asn), rs2040580789, ClinGen CA389793692, ClinVar RCV002782690, ClinVar RCV003777749, AlphaMissense 0.85, MetaLR 0.98, Uncertain significance, Inborn genetic diseases; Dystonia 5; GTP cyclohydrolase I deficiency
- K93R (p.Lys93Arg), TOPMed rs960988987, gnomAD rs960988987, REVEL 0.48, CADD 23.50, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- T94A (p.Thr94Ala), rs2504539278, ClinGen CA389793688, ClinVar RCV003813013, Uncertain significance, GTP cyclohydrolase I deficiency; Dystonia 5
- T94K (p.Thr94Lys), rs1566687244, ClinGen CA389793681, ClinVar RCV000689484, Ensembl rs1566687244, AlphaMissense 0.99, MetaLR 1.00, Likely pathogenic, Dystonia 5; GTP cyclohydrolase I deficiency
- T94M (p.Thr94Met), rs1566687244, ClinGen CA389793683, ClinVar RCV001004083, ClinVar RCV003769402, AlphaMissense 0.99, MetaLR 1.00, Likely pathogenic, Dystonia 5; GTP cyclohydrolase I deficiency
- T94P (p.Thr94Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P95L (p.Pro95Leu), rs886042892, ClinGen CA10604824, NCI-TCGA Cosmic COSV9958, cosmic curated COSV99581, AlphaMissense 0.99, MetaLR 1.00, Uncertain significance, not provided
- W96* (p.Trp96Ter), rs1482120639, ClinGen CA389793669, ClinVar RCV002468715, TOPMed rs1482120639, CADD 41.00, Pathogenic
- W96C (p.Trp96Cys), Ensembl rs938156011, REVEL 0.81, CADD 24.30
- R97T (p.Arg97Thr), Ensembl rs1181621238
- R97W (p.Arg97Trp), rs2140127094, ClinGen CA389793658, ClinVar RCV002035546, Ensembl rs2140127094, AlphaMissense 0.99, MetaLR 1.00, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- A98T (p.Ala98Thr), Ensembl rs1363384428
- A98V (p.Ala98Val), rs2040580445, ClinGen CA389793641, cosmic curated COSV54301, ClinVar RCV001206760, AlphaMissense 0.76, MetaLR 0.93, Pathogenic, GTP cyclohydrolase I deficiency; Dystonia 5
- A99P (p.Ala99Pro), rs1566687219, ClinGen CA389793635, ClinVar RCV002224401, ClinVar RCV003774655, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, not provided; Dystonia 5; GTP cyclohydrolase I deficiency
- A99S (p.Ala99Ser), rs1566687219, ClinGen CA389793631, ClinVar RCV000711752, Ensembl rs1566687219, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, not provided
- S100L (p.Ser100Leu), rs527416949, ClinGen CA260531733, cosmic curated COSV54301, ClinVar RCV001910908, REVEL 0.38, CADD 23.90, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency with hyperphenylalaninemia; GTP cycl
- S100P (p.Ser100Pro), rs2504539183, ClinGen CA389793617, ClinVar RCV002994093, Uncertain significance, Dystonia 5; GTP cyclohydrolase I deficiency
- A101T (p.Ala101Thr), rs1064796560, ClinGen CA16619875, ClinVar RCV000481039, ClinVar RCV004767297, REVEL 0.83, CADD 26.60, Uncertain significance, not specified; not provided
- A101V (p.Ala101Val), NCI-TCGA Cosmic COSV5430, cosmic curated COSV54304, SIFT 0.00, Variant assessed as somatic; moderate impact.
- M102K (p.Met102Lys), UniProt VAR 002637, Pathogenic, in DRD
- M102R (p.Met102Arg), UniProt VAR 016893, Pathogenic, in DRD
Public GCH1 analysis runs
- GCH1 analysis run — GCH1 (552 variants) — completed 2026-08-22