GLA (Alpha-galactosidase A) variants and mutations
GLA (also known as Alpha-galactosidase A) is a human protein-coding gene encoding an alpha-galactosidase A protein. It removes terminal alpha-galactose residues from glycosphingolipids during lysosomal degradation. Loss-of-function variants cause Fabry disease, with progressive accumulation of globotriaosylceramide-related lipids in vascular, renal, cardiac, and nervous tissues. This analysis covers 1,077 GLA variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes Fabry disease, cardiomyopathy, and Angiokeratoma corporis diffusum. Example GLA variants include M1A, M1I, and M1K.
Variant analysis overview
- Gene: GLA
- Protein: Alpha-galactosidase A
- UniProt accession: P06280
- Organism: Homo sapiens
- Variants analyzed: 1077
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 845 unspecified-consequence records; 14 frameshift variants; 115 missense variants; 78 synonymous variants; 2 stop lost; 5 stop-gained variants; 1 in-frame deletions; 1 in-frame insertions; 4 splice-region variants; 12 substitution
- Prediction scores: 825 variants have prediction scores (77% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Fabry disease, cardiomyopathy, Angiokeratoma corporis diffusum, Abnormality of the cardiovascular system, hypertrophic cardiomyopathy, Renal insufficiency, familial hypertrophic cardiomyopathy, stroke disorder, Stroke, kidney failure, acute kidney injury, ischemic stroke.
Protein structure and variant hotspots
- Protein features: 1 binding sites; 3 post-translational modification sites.
- PTM context: 7 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 GLA variants
Examples include M1A, M1I, M1K, M1L, M1T, M1V, Q2*, Q2H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1A (p.Met1Ala), rs2147487930, ClinGen CA2573159130, ClinVar RCV001939379, Pathogenic
- M1I (p.Met1Ile), rs2147487910, ClinGen CA413937941, ClinVar RCV001375575, ClinVar RCV004629626, MetaLR 0.98, MetaSVM 1.59, Pathogenic/Likely pathogenic, Cardiovascular phenotype; Fabry disease; not provided
- M1K (p.Met1Lys), rs1555987232, ClinGen CA413937946, ClinVar RCV002246498, MetaLR 0.99, MetaSVM 1.59, Pathogenic, Fabry disease
- M1L (p.Met1Leu), rs869312265, ClinVar RCV005644566, MetaLR 0.98, MetaSVM 1.46, Pathogenic, Fabry disease
- M1T (p.Met1Thr), rs1555987232, ClinGen CA413937947, ClinVar RCV000586866, ClinVar RCV000731977, MetaLR 0.99, MetaSVM 1.59, Pathogenic, not provided; Fabry disease
- M1V (p.Met1Val), rs869312265, ClinGen CA352616, ClinVar RCV001783375, ClinVar RCV003375362, MetaLR 0.98, MetaSVM 1.46, Pathogenic/Likely pathogenic, Cardiovascular phenotype; not provided; Fabry disease
- Q2* (p.Gln2Ter), rs869312313, ClinGen CA352509, ClinVar RCV001293580, Ensembl rs869312313, Pathogenic
- Q2H (p.Gln2His), rs782748047, ClinGen CA413937924, ClinVar RCV003858544, REVEL 0.17, MetaLR 0.98, Uncertain significance, Fabry disease
- Q2L (p.Gln2Leu), rs782386191, ClinGen CA413937929, ClinVar RCV004520633, AlphaMissense 0.06, MetaLR 0.98, Likely benign, Cardiovascular phenotype
- Q2P (p.Gln2Pro), ExAC rs782386191, gnomAD rs782386191, REVEL 0.18, AlphaMissense 0.06, Uncertain significance, Fabry disease
- Q2R (p.Gln2Arg), rs782386191, ClinGen CA413937928, ClinVar RCV003072956, ExAC rs782386191, AlphaMissense 0.06, MetaLR 0.98, Uncertain significance, Fabry disease
- L3P (p.Leu3Pro), rs150547672, ClinGen CA022172, ClinVar RCV000035313, ClinVar RCV000209183, REVEL 0.22, MetaLR 0.98, Benign/Likely benign, Cardiovascular phenotype; not specified; not provided
- L3V (p.Leu3Val), rs869312133, ClinGen CA353175, ClinVar RCV000209209, ClinVar RCV000209475, AlphaMissense 0.07, MetaLR 0.98, Uncertain significance, Fabry disease
- R4M (p.Arg4Met), rs1569306260, ClinGen CA413937905, ClinVar RCV000709852, Ensembl rs1569306260, AlphaMissense 0.17, MetaLR 0.98, Uncertain significance, Fabry disease
- N5D (p.Asn5Asp), rs782442966, ClinGen CA030007, ClinVar RCV001190922, ClinVar RCV005841531, REVEL 0.17, MetaLR 0.98, Conflicting interpretations, Cardiovascular phenotype; Fabry disease
- N5S (p.Asn5Ser), Ensembl rs1928600420
- P6R (p.Pro6Arg), rs1928600137, ClinGen CA413937876, ClinVar RCV001372488, ClinVar RCV002413896, AlphaMissense 0.04, MetaLR 0.98, Uncertain significance, Cardiovascular phenotype; Fabry disease
- E7* (p.Glu7Ter), rs398123207, ClinGen CA021598, ClinVar RCV000078272, ClinVar RCV002498376, Pathogenic
- E7D (p.Glu7Asp), rs1555987217, ClinGen CA413937858, ClinVar RCV003030100, gnomAD rs1555987217, REVEL 0.28, MetaLR 0.98, Uncertain significance, Fabry disease
- E7N (p.Glu7Asn), rs2147487830, ClinGen CA2573159129, ClinVar RCV001943235, ClinVar RCV003303377, Pathogenic
- E7Q (p.Glu7Gln), rs398123207, ClinGen CA413937868, ClinVar RCV004016452, Uncertain significance, Fabry disease
- H9L (p.His9Leu), NCI-TCGA Cosmic COSV9951, Variant assessed as somatic; moderate impact.
- H9R (p.His9Arg), rs1555987214, ClinGen CA413937839, ClinVar RCV001090391, ClinVar RCV001184278, REVEL 0.22, MetaLR 0.98, Conflicting interpretations, not provided; Fabry disease
- H9Y (p.His9Tyr), rs2520947587, ClinGen CA413937842, ClinVar RCV003093740, Uncertain significance, Fabry disease
- L10P (p.Leu10Pro), rs2520947474, ClinGen CA413937826, ClinVar RCV003003298, Uncertain significance, Fabry disease
- L10V (p.Leu10Val), TOPMed rs727503073, Likely benign
- G11A (p.Gly11Ala), rs782498765, ClinGen CA030516, ClinVar RCV002576773, ExAC rs782498765, REVEL 0.17, MetaLR 0.98, Uncertain significance, Fabry disease
- G11C (p.Gly11Cys), NCI-TCGA Cosmic COSV9951, Variant assessed as somatic; moderate impact.
- G11D (p.Gly11Asp), ExAC rs782498765, gnomAD rs782498765, REVEL 0.47, MetaLR 0.98, Uncertain significance
- G11R (p.Gly11Arg), TOPMed rs1367502468, gnomAD rs1367502468, REVEL 0.43, MetaLR 0.99, Uncertain significance, Fabry disease
- G11S (p.Gly11Ser), TOPMed rs1367502468, gnomAD rs1367502468, REVEL 0.17, MetaLR 0.98
- G11V (p.Gly11Val), rs782498765, ClinGen CA413937813, ClinVar RCV001183430, ClinVar RCV006279414, REVEL 0.20, MetaLR 0.98, Uncertain significance, not provided; Fabry disease
- C12* (p.Cys12Ter), rs869312283, NCI-TCGA Cosmic COSV9951, ClinVar RCV005644724, gnomAD rs869312283, Pathogenic
- C12F (p.Cys12Phe), rs2520947238, ClinGen CA413937798, ClinVar RCV003313425, ClinVar RCV004333263, REVEL 0.33, MetaLR 0.98, Uncertain significance, Cardiovascular phenotype; not provided; Fabry disease
- A13S (p.Ala13Ser), NCI-TCGA Cosmic COSV5450, Variant assessed as somatic; moderate impact.
- A13T (p.Ala13Thr), rs2147487725, ClinGen CA413937793, ClinVar RCV001525252, Ensembl rs2147487725, REVEL 0.19, MetaLR 0.98, Uncertain significance, Fabry disease
- A13V (p.Ala13Val), rs869312297, NCI-TCGA Cosmic COSV5451, ClinVar RCV005645692, Ensembl rs869312297, AlphaMissense 0.07, MetaLR 0.98, Uncertain significance, Fabry disease
- L14F (p.Leu14Phe), rs2147487699, ClinGen CA413937779, ClinVar RCV001878314, Ensembl rs2147487699, AlphaMissense 0.06, MetaLR 0.98, Uncertain significance, Fabry disease
- L14P (p.Leu14Pro), rs730880455, ClinGen CA021708, ClinVar RCV000734825, ClinVar RCV001192396, AlphaMissense 0.10, MetaLR 0.99, Pathogenic
- A15E (p.Ala15Glu), rs869312304, ClinGen CA352491, ClinVar RCV003041471, TOPMed rs869312304, AlphaMissense 0.23, MetaLR 0.98, Pathogenic, Fabry disease
- A15P (p.Ala15Pro), rs869312303, ClinVar RCV005644868, gnomAD rs869312303, AlphaMissense 0.09, MetaLR 0.98, Likely pathogenic, Fabry disease
- A15T (p.Ala15Thr), rs869312303, ClinGen CA413937768, ClinVar RCV001176575, gnomAD rs869312303, REVEL 0.28, AlphaMissense 0.09, Uncertain significance, Fabry disease
- A15V (p.Ala15Val), rs869312304, ClinGen CA413937757, ClinVar RCV004015594, TOPMed rs869312304, REVEL 0.26, AlphaMissense 0.23, Uncertain significance, Fabry disease
- L16P (p.Leu16Pro), rs869312310, ClinGen CA413937741, ClinVar RCV002337874, ClinVar RCV003096472, AlphaMissense 0.14, MetaLR 0.99, Pathogenic/Likely pathogenic, Cardiovascular phenotype; Fabry disease
- L16R (p.Leu16Arg), rs869312310, ClinVar RCV005644892, Ensembl rs869312310, AlphaMissense 0.14, MetaLR 0.99, Likely pathogenic, Fabry disease
- L16V (p.Leu16Val), Ensembl rs869312309
- F18L (p.Phe18Leu), rs2520946586, ClinGen CA413937720, ClinVar RCV003391530, Uncertain significance, GLA-related disorder
- F18S (p.Phe18Ser), rs2147487622, ClinGen CA413937712, ClinVar RCV001794976, ClinVar RCV005645305, AlphaMissense 0.13, MetaLR 0.99, Pathogenic, not provided; Fabry disease
- L19P (p.Leu19Pro), rs1928592578, ClinGen CA413937689, ClinVar RCV001174874, Ensembl rs1928592578, AlphaMissense 0.09, MetaLR 0.99, Conflicting interpretations, Fabry disease
- L19Q (p.Leu19Gln), rs1928592578, ClinGen CA413937691, ClinVar RCV001293632, ClinVar RCV005645250, AlphaMissense 0.09, MetaLR 0.99, Conflicting interpretations, not specified; Fabry disease
- A20D (p.Ala20Asp), rs869312134, ClinGen CA353016, ClinVar RCV000208891, ClinVar RCV000209573, AlphaMissense 0.23, MetaLR 0.99, Pathogenic/Likely pathogenic, Fabry disease
- A20P (p.Ala20Pro), rs104894847, ClinGen CA021802, ClinVar RCV000011511, ClinVar RCV005644481, AlphaMissense 0.10, MetaLR 0.99, Pathogenic, Fabry disease
- L21F (p.Leu21Phe), rs782164084, ClinGen CA031556, ClinVar RCV001789803, ExAC rs782164084, REVEL 0.25, MetaLR 0.99, Conflicting interpretations, Fabry disease
- L21P (p.Leu21Pro), rs869312135, ClinGen CA353214, ClinVar RCV000209283, ClinVar RCV000209546, REVEL 0.68, MetaLR 0.99, Pathogenic/Likely pathogenic, Fabry disease
- V22G (p.Val22Gly), Ensembl rs869312379
- V22I (p.Val22Ile), rs2520946121, ClinGen CA413937646, ClinVar RCV003511070, ClinVar RCV005628386, REVEL 0.21, MetaLR 0.98, Uncertain significance, Cardiovascular phenotype; Fabry disease
- W24* (p.Trp24Ter), rs869312390, ClinVar RCV005644725, Ensembl rs869312390, Pathogenic
- W24C (p.Trp24Cys), rs869312392, ClinGen CA413937581, ClinVar RCV001193672, ClinVar RCV005645220, AlphaMissense 0.18, MetaLR 0.98, Uncertain significance, Fabry disease
- W24R (p.Trp24Arg), rs397515871, ClinGen CA021990, ClinVar RCV000035308, ClinVar RCV000769544, REVEL 0.40, MetaLR 0.99, Uncertain significance, Cardiovascular phenotype; not provided; Cardiomyopathy
- D25G (p.Asp25Gly), rs1336588430, ClinGen CA413937566, ClinVar RCV004015473, REVEL 0.24, AlphaMissense 0.09, Uncertain significance, Fabry disease
- D25N (p.Asp25Asn), rs781788693, ClinGen CA031966, ClinVar RCV001183525, ClinVar RCV001256948, AlphaMissense 0.08, MetaLR 0.98, Uncertain significance, Hypertrophic cardiomyopathy 1; Fabry disease
- D25V (p.Asp25Val), rs1336588430, ClinGen CA413937563, ClinVar RCV002391606, ClinVar RCV005097117, AlphaMissense 0.09, MetaLR 0.99, Uncertain significance, Cardiovascular phenotype; Fabry disease
- D25Y (p.Asp25Tyr), rs781788693, ClinGen CA413937576, ClinVar RCV002671696, AlphaMissense 0.08, MetaLR 0.98, Uncertain significance, Fabry disease
- I26F (p.Ile26Phe), Ensembl rs869312397
- A29D (p.Ala29Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A29P (p.Ala29Pro), rs142449183, ClinGen CA413937484, ClinVar RCV003510067, AlphaMissense 0.08, MetaLR 0.98, Uncertain significance, Fabry disease
- A29S (p.Ala29Ser), rs142449183, ClinGen CA413937480, ClinVar RCV001187973, ClinVar RCV001751339, REVEL 0.28, AlphaMissense 0.08, Uncertain significance, not provided; Fabry disease; Cardiovascular phenotype
- A29T (p.Ala29Thr), rs142449183, ClinGen CA032260, ClinVar RCV000817399, ESP rs142449183, REVEL 0.26, AlphaMissense 0.08, Uncertain significance, Fabry disease
- R30T (p.Arg30Thr), ExAC rs782079853, gnomAD rs782079853, REVEL 0.20, MetaLR 0.98
- A31G (p.Ala31Gly), rs869312448, ClinGen CA413937438, ClinVar RCV001773184, Ensembl rs869312448, AlphaMissense 0.23, MetaLR 0.99, Uncertain significance, Fabry disease; not provided
- A31V (p.Ala31Val), rs869312448, ClinGen CA352530, ClinVar RCV001293631, UniProt VAR 012363, AlphaMissense 0.23, MetaLR 0.99, Pathogenic/Likely pathogenic, Fabry disease
- L32P (p.Leu32Pro), rs1569306168, ClinGen CA413937429, ClinVar RCV000727580, ClinVar RCV003509593, AlphaMissense 0.49, MetaLR 1.00, Pathogenic/Likely pathogenic, Fabry disease; not provided; Cardiovascular phenotype
- L32V (p.Leu32Val), rs1928587825, ClinGen CA413937432, ClinVar RCV001341302, Ensembl rs1928587825, AlphaMissense 0.18, MetaLR 1.00, Uncertain significance, Fabry disease
- D33G (p.Asp33Gly), rs869312136, ClinGen CA353071, ClinVar RCV000208990, ClinVar RCV000209255, AlphaMissense 0.16, MetaLR 1.00, Likely pathogenic, Fabry disease
- D33N (p.Asp33Asn), rs2147487414, ClinGen CA413937424, ClinVar RCV001355414, Ensembl rs2147487414, AlphaMissense 0.11, MetaLR 0.99, Uncertain significance, not provided
- N34D (p.Asn34Asp), rs1555987150, ClinGen CA413937393, ClinVar RCV000593782, ClinVar RCV005645108, AlphaMissense 0.40, MetaLR 1.00, Conflicting interpretations, not provided; Fabry disease
- N34S (p.Asn34Ser), rs104894835, ClinGen CA021300, ClinVar RCV000011471, ClinVar RCV000723530, AlphaMissense 0.23, MetaLR 1.00, Pathogenic, in FABRYD
- G35E (p.Gly35Glu), rs869312137, ClinGen CA353058, ClinVar RCV000208963, ClinVar RCV000209648, AlphaMissense 0.35, MetaLR 1.00, Likely pathogenic, Fabry disease
- G35R (p.Gly35Arg), UniProt VAR 000433, Likely pathogenic, Fabry disease
- L36W (p.Leu36Trp), rs869312138, ClinGen CA353241, ClinVar RCV000209353, ClinVar RCV000209629, AlphaMissense 0.39, MetaLR 1.00, Pathogenic, Fabry disease
- A37P (p.Ala37Pro), rs869312226, ClinGen CA413937322, ClinVar RCV000685810, ClinVar RCV000734407, AlphaMissense 0.68, MetaLR 1.00, Pathogenic/Likely pathogenic, Fabry disease; not provided
- A37T (p.Ala37Thr), rs869312226, ClinGen CA352666, NCI-TCGA Cosmic COSV5451, ClinVar RCV001782190, AlphaMissense 0.68, MetaLR 1.00, Likely pathogenic, not provided; Fabry disease
- R38G (p.Arg38Gly), rs730880446, ClinGen CA021410, ClinVar RCV000157892, ClinVar RCV001850199, AlphaMissense 0.15, MetaLR 0.99, Uncertain significance
- R38K (p.Arg38Lys), Ensembl rs869312231
- T39M (p.Thr39Met), rs201819574, NCI-TCGA Cosmic COSV5450, 1000Genomes rs201819574, ExAC rs201819574, REVEL 0.87, AlphaMissense 0.09, Uncertain significance, Fabry disease
- T39R (p.Thr39Arg), rs201819574, ClinGen CA413937260, ClinVar RCV003484242, AlphaMissense 0.09, MetaLR 1.00, Likely pathogenic, Fabry disease
- P40A (p.Pro40Ala), rs104894831, ClinGen CA413937249, ClinVar RCV003050639, AlphaMissense 0.83, MetaLR 1.00, Conflicting interpretations, Fabry disease
- P40L (p.Pro40Leu), rs398123199, ClinGen CA413937240, ClinVar RCV000781427, UniProt VAR 012364, AlphaMissense 0.84, MetaLR 1.00, Pathogenic/Likely pathogenic, Fabry disease
- P40R (p.Pro40Arg), rs398123199, ClinGen CA021455, ClinVar RCV000078264, ClinVar RCV003997194, AlphaMissense 0.84, MetaLR 1.00, Pathogenic, in FABRYD
- P40S (p.Pro40Ser), rs104894831, ClinGen CA021436, ClinVar RCV000011466, ClinVar RCV000729403, AlphaMissense 0.83, MetaLR 1.00, Pathogenic, not provided; Fabry disease
- T41S (p.Thr41Ser), rs782362194, ClinGen CA029760, ClinVar RCV001181362, ClinVar RCV002363037, REVEL 0.74, MetaLR 0.99, Conflicting interpretations, Cardiovascular phenotype; not provided; Fabry disease
- M42I (p.Met42Ile), rs1569306108, ClinGen CA413937183, ClinVar RCV000729336, ClinVar RCV005645164, AlphaMissense 0.85, MetaLR 0.99, Likely pathogenic, not provided; Fabry disease
- M42L (p.Met42Leu), rs797044613, ClinGen CA021494, ClinVar RCV000235742, ClinVar RCV000809963, REVEL 0.93, AlphaMissense 0.27, Pathogenic, in FABRYD
- M42T (p.Met42Thr), rs398123201, ClinGen CA021500, ClinVar RCV000078266, ClinVar RCV000723538, AlphaMissense 0.58, MetaLR 0.99, Pathogenic, in FABRYD
- M42V (p.Met42Val), rs797044613, ClinGen CA352279, ClinVar RCV000727558, ClinVar RCV001063224, AlphaMissense 0.27, MetaLR 0.99, Pathogenic, not provided; Fabry disease
- G43A (p.Gly43Ala), rs797044500, ClinGen CA273346, ClinVar RCV000153325, ClinVar RCV001193673, Pathogenic, in FABRYD
- G43R (p.Gly43Arg), rs886044906, ClinGen CA413937174, ClinVar RCV001956188, UniProt VAR 062552, AlphaMissense 0.98, MetaLR 1.00, Pathogenic, Fabry disease
- G43S (p.Gly43Ser), rs886044906, ClinGen CA10606899, ClinVar RCV000298627, ClinVar RCV005645068, AlphaMissense 0.98, MetaLR 1.00, Pathogenic/Likely pathogenic, not provided; Fabry disease
- G43V (p.Gly43Val), rs1928583820, ClinGen CA413937161, ClinVar RCV001193639, Ensembl rs1928583820, AlphaMissense 0.95, MetaLR 1.00, Pathogenic, Fabry disease
- W44* (p.Trp44Ter), rs398123202, ClinGen CA413937130, ClinVar RCV000730691, Ensembl rs398123202, AlphaMissense 0.99, MetaLR 1.00, Pathogenic
- W44C (p.Trp44Cys), rs398123202, ClinGen CA413937124, ClinVar RCV000588414, ClinVar RCV001807298, AlphaMissense 0.99, MetaLR 1.00, Conflicting interpretations, not provided; Fabry disease
- L45P (p.Leu45Pro), UniProt VAR 077373, Pathogenic, Fabry disease
- L45V (p.Leu45Val), rs143084761, ClinGen CA413937116, ClinVar RCV003623551, NCI-TCGA TCGA novel, Uncertain significance, Fabry disease
- H46A (p.His46Ala), rs2147487148, ClinGen CA2573055058, ClinVar RCV001754536, Likely pathogenic, in FABRYD
- H46L (p.His46Leu), rs398123203, ClinGen CA021538, ClinVar RCV000078268, ClinVar RCV005644507, AlphaMissense 0.84, MetaLR 0.99, Pathogenic, in FABRYD
- H46P (p.His46Pro), rs398123203, ClinGen CA413937084, ClinVar RCV003066356, ClinVar RCV003491211, AlphaMissense 0.84, MetaLR 0.99, Likely pathogenic, Fabry disease; not provided
- H46Q (p.His46Gln), rs869312253, ClinGen CA352995, ClinVar RCV001193643, ClinVar RCV005645038, AlphaMissense 0.65, MetaLR 0.99, Uncertain significance, Fabry disease
- H46R (p.His46Arg), rs398123203, ClinGen CA021532, ClinVar RCV000173078, ClinVar RCV005645031, AlphaMissense 0.84, MetaLR 0.99, Pathogenic, in FABRYD
- H46Y (p.His46Tyr), rs1928582757, ClinGen CA413937089, ClinVar RCV001280630, UniProt VAR 012368, AlphaMissense 0.48, MetaLR 0.99, Pathogenic, Fabry disease
- W47C (p.Trp47Cys), rs1555987101, ClinGen CA413937045, ClinVar RCV000627817, ClinVar RCV003488739, AlphaMissense 0.98, MetaLR 1.00, Likely pathogenic, Fabry disease
- W47G (p.Trp47Gly), UniProt VAR 012369, Pathogenic, Fabry disease
- W47R (p.Trp47Arg), UniProt VAR 076478, Pathogenic/Likely pathogenic, not provided; Fabry disease
- E48D (p.Glu48Asp), rs869312254, ClinVar RCV005645761, UniProt VAR 077374, Ensembl rs869312254, AlphaMissense 0.84, MetaLR 0.99, Likely pathogenic, Fabry disease
- E48Q (p.Glu48Gln), rs398123204, ClinGen CA021544, ClinVar RCV000078269, ClinVar RCV005644508, AlphaMissense 0.18, MetaLR 0.99, Pathogenic, in FABRYD
- R49L (p.Arg49Leu), UniProt VAR 000435, Pathogenic, Fabry disease
- R49P (p.Arg49Pro), rs398123205, ClinGen CA021552, ClinVar RCV000078270, ClinVar RCV003509487, AlphaMissense 0.95, MetaLR 0.99, Pathogenic, in FABRYD
- R49S (p.Arg49Ser), rs2520943698, ClinGen CA413937009, ClinVar RCV003135372, ClinVar RCV005645450, Pathogenic/Likely pathogenic, not provided; Fabry disease
- F50L (p.Phe50Leu), NCI-TCGA Cosmic COSV9951, Variant assessed as somatic; moderate impact.
- M51I (p.Met51Ile), rs869312255, ClinGen CA352950, ClinVar RCV001193644, Ensembl rs869312255, AlphaMissense 0.32, MetaLR 0.99, Likely pathogenic, Fabry disease
- M51L (p.Met51Leu), rs1569306069, ClinGen CA413936939, ClinVar RCV000681675, ClinVar RCV000797100, AlphaMissense 0.08, MetaLR 0.97, Uncertain significance, Fabry disease
- M51V (p.Met51Val), rs1569306069, ClinGen CA413936946, NCI-TCGA Cosmic COSV5450, ClinVar RCV003324310, AlphaMissense 0.08, MetaLR 0.97, Uncertain significance, not specified; not provided
- C52G (p.Cys52Gly), rs1057521047, ClinGen CA413936907, ClinVar RCV001193640, Ensembl rs1057521047, AlphaMissense 0.77, MetaLR 0.99, Pathogenic/Likely pathogenic, Fabry disease
- C52R (p.Cys52Arg), rs1057521047, ClinGen CA16609111, ClinVar RCV000424225, ClinVar RCV001807250, AlphaMissense 0.77, MetaLR 0.99, Pathogenic, not provided; Fabry disease
- C52S (p.Cys52Ser), rs869312256, ClinVar RCV005644869, UniProt VAR 000437, Ensembl rs869312256, AlphaMissense 0.96, MetaLR 0.99, Pathogenic, Fabry disease
- N53K (p.Asn53Lys), Ensembl rs869312257, Uncertain significance, Fabry disease
- N53S (p.Asn53Ser), rs1928580573, ClinGen CA413936862, ClinVar RCV001338831, Ensembl rs1928580573, AlphaMissense 0.08, MetaLR 0.96, Uncertain significance, Fabry disease
- N53Y (p.Asn53Tyr), NCI-TCGA Cosmic COSV5451, Uncertain significance, Fabry disease
- L54I (p.Leu54Ile), NCI-TCGA Cosmic COSV5450, Variant assessed as somatic; moderate impact.
- C56F (p.Cys56Phe), rs869312258, ClinGen CA352731, ClinVar RCV001193044, ClinVar RCV005348077, AlphaMissense 0.84, MetaLR 0.99, Conflicting interpretations, Cardiovascular phenotype; not specified; Fabry disease
- C56G (p.Cys56Gly), rs104894836, ClinGen CA021558, ClinVar RCV000011472, UniProt VAR 000439, AlphaMissense 0.76, MetaLR 0.99, Pathogenic, Fabry disease
- C56Y (p.Cys56Tyr), rs869312258, ClinGen CA352477, ClinVar RCV001379650, UniProt VAR 012372, AlphaMissense 0.84, MetaLR 0.99, Pathogenic, Fabry disease
- Q57* (p.Gln57Ter), rs869312259, ClinGen CA352869, ClinVar RCV001194305, ClinVar RCV004596111, Pathogenic
- Q57P (p.Gln57Pro), rs869312260, ClinGen CA413936796, ClinVar RCV001563580, Ensembl rs869312260, AlphaMissense 0.06, MetaLR 0.93, Likely pathogenic, Fabry disease
- Q57R (p.Gln57Arg), rs869312260, ClinGen CA352488, ClinVar RCV001762947, ClinVar RCV005645292, REVEL 0.20, AlphaMissense 0.06, Conflicting interpretations, not provided; Fabry disease
- E59K (p.Glu59Lys), UniProt VAR 000440, Pathogenic, Fabry disease
- E59V (p.Glu59Val), rs2520943061, ClinGen CA413936733, ClinVar RCV003622772, Likely pathogenic, Fabry disease
- P60L (p.Pro60Leu), rs869312262, ClinGen CA352942, ClinVar RCV000731360, ClinVar RCV003509514, REVEL 0.85, MetaLR 0.98, Uncertain significance, not provided; Cardiovascular phenotype; Fabry disease
- P60S (p.Pro60Ser), rs727504689, ClinGen CA413936715, NCI-TCGA Cosmic COSV5451, ClinVar RCV001784081, AlphaMissense 0.11, MetaLR 0.99, Conflicting interpretations, not provided; Fabry disease
- P60T (p.Pro60Thr), rs727504689, ClinGen CA021565, ClinVar RCV000155963, ClinVar RCV003998296, AlphaMissense 0.11, MetaLR 0.99, Likely pathogenic, in FABRYD
- D61H (p.Asp61His), rs1928578650, ClinGen CA413936689, ClinVar RCV003239279, AlphaMissense 0.07, MetaLR 0.99, Uncertain significance, Fabry disease
- D61N (p.Asp61Asn), rs1928578650, ClinGen CA413936694, ClinVar RCV001176589, Ensembl rs1928578650, REVEL 0.36, AlphaMissense 0.07, Uncertain significance, Fabry disease
- S62F (p.Ser62Phe), rs1603047699, ClinGen CA413936652, ClinVar RCV000806353, Ensembl rs1603047699, AlphaMissense 0.14, MetaLR 0.99, Uncertain significance, Fabry disease
- C63R (p.Cys63Arg), rs1928578294, ClinGen CA413936636, ClinVar RCV001290654, ClinVar RCV005645249, AlphaMissense 0.92, MetaLR 0.99, Conflicting interpretations, not specified; Fabry disease
- C63Y (p.Cys63Tyr), rs1569306022, ClinGen CA413936631, ClinVar RCV000730949, ClinVar RCV002535181, AlphaMissense 0.93, MetaLR 0.99, Pathogenic, not provided; Fabry disease
- I64F (p.Ile64Phe), rs869312139, ClinGen CA353104, ClinVar RCV000209059, ClinVar RCV000209447, AlphaMissense 0.46, MetaLR 1.00, Likely pathogenic, Fabry disease
- S65G (p.Ser65Gly), rs1569306013, ClinGen CA413936576, NCI-TCGA Cosmic COSV5450, ClinVar RCV000733743, AlphaMissense 0.10, MetaLR 1.00, Uncertain significance, not provided
- S65T (p.Ser65Thr), rs104894848, ClinGen CA021577, ClinVar RCV000011513, UniProt VAR 032290, AlphaMissense 0.20, MetaLR 1.00, Likely pathogenic, Fabry disease
- E66G (p.Glu66Gly), rs869312264, ClinGen CA352977, ClinVar RCV003487869, ClinVar RCV003779245, REVEL 0.98, MetaLR 1.00, Likely pathogenic, Fabry disease; not provided
- E66Q (p.Glu66Gln), rs104894833, ClinGen CA021590, ClinVar RCV000011470, ClinVar RCV000150750, REVEL 0.93, MetaLR 1.00, Pathogenic, Fabry disease
- L68F (p.Leu68Phe), rs1928411447, ClinGen CA413934691, ClinVar RCV001060432, ClinVar RCV002418513, AlphaMissense 0.52, MetaLR 1.00, Pathogenic/Likely pathogenic, Cardiovascular phenotype; Fabry disease
- M70T (p.Met70Thr), rs2520914915, ClinGen CA413934557, ClinVar RCV003510969, Uncertain significance, Fabry disease
- M70V (p.Met70Val), rs1555986330, ClinGen CA413934581, ClinVar RCV001525958, ClinVar RCV003130534, REVEL 0.52, MetaLR 0.98, Uncertain significance, Fabry disease; not provided
- E71G (p.Glu71Gly), rs781927744, ClinGen CA030441, ClinVar RCV000209041, ClinVar RCV000209598, REVEL 0.57, MetaLR 0.99, Uncertain significance, not provided; Fabry disease
- M72T (p.Met72Thr), rs1569304920, ClinGen CA413934453, ClinVar RCV003062810, Ensembl rs1569304920, AlphaMissense 0.21, MetaLR 0.99, Conflicting interpretations, Fabry disease
- M72V (p.Met72Val), UniProt VAR 000442, Likely pathogenic, Fabry disease
- E74D (p.Glu74Asp), Ensembl rs869312266
- E74K (p.Glu74Lys), rs2147480899, ClinGen CA413934375, ClinVar RCV001761126, Ensembl rs2147480899, AlphaMissense 0.08, MetaLR 0.99, Uncertain significance, not provided
- M76I (p.Met76Ile), rs2520914690, ClinGen CA413934308, ClinVar RCV004015551, Uncertain significance, Fabry disease
- M76T (p.Met76Thr), rs2520914744, ClinGen CA16602197, ClinVar RCV003066355, ClinVar RCV003491210, Conflicting interpretations, Fabry disease; not provided
- S78* (p.Ser78Ter), rs869312268, ClinVar RCV005644732, Ensembl rs869312268, Pathogenic
- E79* (p.Glu79Ter), rs730880443, ClinGen CA021605, ClinVar RCV000733596, ClinVar RCV002516375, Pathogenic
- G80A (p.Gly80Ala), rs781838005, ClinGen CA413934107, ClinVar RCV001563581, 1000Genomes rs781838005, REVEL 0.96, MetaLR 1.00, Uncertain significance, Fabry disease
- G80C (p.Gly80Cys), Ensembl rs1603044130, Uncertain significance, in FABRYD
- G80D (p.Gly80Asp), rs781838005, ClinGen CA089420, ClinVar RCV000209421, ClinVar RCV000209815, REVEL 0.96, MetaLR 1.00, Conflicting interpretations, Cardiovascular phenotype; not provided; Fabry disease
- G80V (p.Gly80Val), NCI-TCGA Cosmic COSV5450, Uncertain significance, in FABRYD
- W81* (p.Trp81Ter), rs398123208, ClinGen CA021611, ClinVar RCV000157886, ClinVar RCV001807017, AlphaMissense 0.91, MetaLR 1.00, Pathogenic
- W81S (p.Trp81Ser), rs398123208, ClinGen CA413934061, ClinVar RCV001328356, Ensembl rs398123208, AlphaMissense 0.91, MetaLR 1.00, Pathogenic, Fabry disease
- K82* (p.Lys82Ter), rs1057516429, ClinGen CA16042047, ClinVar RCV000411879, Ensembl rs1057516429, Likely pathogenic
- D83N (p.Asp83Asn), rs782722577, ClinGen CA030449, ClinVar RCV000471970, ClinVar RCV000596614, REVEL 0.64, MetaLR 1.00, Conflicting interpretations, not provided; Charcot-Marie-Tooth disease; Cardiovascular phenotype
- G85A (p.Gly85Ala), rs1569304898, ClinGen CA413933910, ClinVar RCV000732723, ClinVar RCV001855691, AlphaMissense 0.53, MetaLR 1.00, Conflicting interpretations, not provided; Fabry disease
- G85D (p.Gly85Asp), rs1569304898, ClinGen CA413933914, ClinVar RCV000730015, ClinVar RCV001855746, AlphaMissense 0.53, MetaLR 1.00, Pathogenic/Likely pathogenic, not provided; Cardiovascular phenotype; Fabry disease
- G85V (p.Gly85Val), rs1569304898, ClinGen CA413933908, ClinVar RCV000730039, ClinVar RCV005645165, AlphaMissense 0.53, MetaLR 1.00, Conflicting interpretations, not provided; Fabry disease
- Y86C (p.Tyr86Cys), UniProt VAR 012373, Pathogenic, Fabry disease
- Y86F (p.Tyr86Phe), Ensembl rs1928408168, Likely pathogenic, Fabry disease
- Y86H (p.Tyr86His), rs869312140, ClinGen CA353138, ClinVar RCV000209126, ClinVar RCV000209399, AlphaMissense 0.91, MetaLR 0.99, Pathogenic, Fabry disease
- E87A (p.Glu87Ala), TOPMed rs1182870909, gnomAD rs1182870909, REVEL 0.62, AlphaMissense 0.15
- E87K (p.Glu87Lys), rs986730205, ClinGen CA333095185, ClinVar RCV001184364, TOPMed rs986730205, REVEL 0.36, MetaLR 0.98, Uncertain significance, Cardiovascular phenotype; Fabry disease
- E87Q (p.Glu87Gln), NCI-TCGA Cosmic COSV9951, Variant assessed as somatic; moderate impact.
- E87V (p.Glu87Val), rs1182870909, ClinGen CA413933833, ClinVar RCV004012577, AlphaMissense 0.15, MetaLR 0.99, Uncertain significance, Fabry disease
- L89F (p.Leu89Phe), rs1555986305, ClinGen CA413933792, ClinVar RCV000525086, ClinVar RCV000590425, AlphaMissense 0.07, MetaLR 0.97, Conflicting interpretations, Fabry disease; not provided
Public GLA analysis runs
- GLA analysis run — GLA (1,077 variants) — completed 2026-08-18