GFAP (Glial fibrillary acidic protein) variants and mutations
GFAP (also known as Glial fibrillary acidic protein) is a human protein-coding gene encoding a glial fibrillary acidic protein. It forms intermediate filaments that support astrocyte structure and help organize responses to injury within the central nervous system. Dominant pathogenic variants cause Alexander disease through toxic accumulation and aggregation of abnormal GFAP in astrocytes. This analysis covers 795 GFAP variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes Alexander disease, hereditary disease, and Alexander disease type I. Example GFAP variants include E2K, E2Q, and R3K.
Variant analysis overview
- Gene: GFAP
- Protein: Glial fibrillary acidic protein
- UniProt accession: P14136
- Organism: Homo sapiens
- Variants analyzed: 795
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 695 unspecified-consequence records; 2 natural variant; 6 stop lost; 1 stop retained variant; 57 missense variants; 6 stop-gained variants; 20 synonymous variants; 2 splice-region variants; 1 in-frame deletions; 2 frameshift variants; 10 substitution
- Prediction scores: 624 variants have prediction scores (78% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Alexander disease, hereditary disease, Alexander disease type I, Seizure, Alexander disease type II, spastic paraplegia, intellectual disability, nystagmus, and obesity, metachromatic leukodystrophy, Progressive ventriculomegaly, scoliosis, Abnormality of the skeletal system, hypertrophic cardiomyopathy, primary ciliary dyskinesia.
Protein structure and variant hotspots
- Protein features: 1 domains; 15 post-translational modification sites.
- Structural context: 538 variants have structural context.
- PTM context: 40 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable GFAP variants
Examples include E2K, E2Q, R3K, R3S, R3T, R4G, R4K, R5C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2K (p.Glu2Lys), cosmic curated COSV10458, CADD 22.70, PolyPhen-2 0.17
- E2Q (p.Glu2Gln), TOPMed rs1211825074, CADD 23.40, PolyPhen-2 0.29
- R3K (p.Arg3Lys), TOPMed rs1250081721, gnomAD rs1250081721
- R3S (p.Arg3Ser), ExAC rs776235455, gnomAD rs776235455, CADD 17.40, PolyPhen-2 0.00
- R3T (p.Arg3Thr), TOPMed rs1250081721, gnomAD rs1250081721, CADD 18.40, PolyPhen-2 0.03
- R4G (p.Arg4Gly), ExAC rs770750986, TOPMed rs770750986, gnomAD rs770750986, CADD 24.10, PolyPhen-2 0.00, Uncertain significance, not provided
- R4K (p.Arg4Lys), Ensembl rs2145643494
- R5C (p.Arg5Cys), rs142049068, ClinGen CA8609136, cosmic curated COSV10587, ClinVar RCV002764154, CADD 25.00, PolyPhen-2 0.25, Uncertain significance, Inborn genetic diseases; not provided
- R5H (p.Arg5His), rs773456179, ClinGen CA8609135, NCI-TCGA Cosmic COSV5364, cosmic curated COSV53649, CADD 22.50, PolyPhen-2 0.00, Uncertain significance, not provided
- I6V (p.Ile6Val), TOPMed rs2051893143, CADD 4.29, PolyPhen-2 0.00
- T7A (p.Thr7Ala), Ensembl rs1567779198, CADD 15.50, PolyPhen-2 0.00
- T7N (p.Thr7Asn), rs748191931, ClinGen CA8609133, ClinVar RCV002750061, ExAC rs748191931, CADD 22.00, PolyPhen-2 0.03, Uncertain significance, not provided
- T7P (p.Thr7Pro), Ensembl rs1567779198
- S8F (p.Ser8Phe), Ensembl rs1476376917
- A9S (p.Ala9Ser), ExAC rs769218064, gnomAD rs769218064, CADD 3.37, PolyPhen-2 0.00
- A9T (p.Ala9Thr), ExAC rs769218064, gnomAD rs769218064, CADD 9.07, PolyPhen-2 0.00
- A9V (p.Ala9Val), 1000Genomes rs202212750, CADD 11.70, PolyPhen-2 0.00
- A10P (p.Ala10Pro), TOPMed rs2051892565
- R11C (p.Arg11Cys), rs749815672, ClinGen CA8609129, ClinVar RCV001288189, ExAC rs749815672, CADD 23.20, PolyPhen-2 0.00, Uncertain significance, not provided
- R11G (p.Arg11Gly), rs749815672, ClinGen CA399849224, ClinVar RCV003221160, ExAC rs749815672, CADD 22.70, PolyPhen-2 0.09, Uncertain significance, Inborn genetic diseases
- R11H (p.Arg11His), rs780481913, ClinGen CA8609128, ClinVar RCV001921246, ExAC rs780481913, CADD 17.60, PolyPhen-2 0.00, Uncertain significance, not provided
- R11P (p.Arg11Pro), rs780481913, ClinGen CA399849223, ClinVar RCV001914113, ExAC rs780481913, CADD 23.40, PolyPhen-2 0.31, Uncertain significance, not provided
- R12C (p.Arg12Cys), rs375692636, ClinGen CA8609127, ClinVar RCV002961292, ClinVar RCV003777999, CADD 24.10, PolyPhen-2 0.01, Conflicting interpretations, Inborn genetic diseases; not provided
- R12G (p.Arg12Gly), rs375692636, ClinGen CA399849220, ClinVar RCV002765796, ClinVar RCV005844103, CADD 25.00, PolyPhen-2 0.35, Uncertain significance, Inborn genetic diseases; not provided
- R12H (p.Arg12His), 1000Genomes rs373706480, ESP rs373706480, ExAC rs373706480, TOPMed rs373706480, CADD 25.10, PolyPhen-2 0.68, Uncertain significance, not provided
- S13F (p.Ser13Phe), TOPMed rs2051892058, gnomAD rs2051892058, CADD 23.40, PolyPhen-2 0.36, Uncertain significance, Inborn genetic diseases
- Y14* (p.Tyr14Ter), 1000Genomes rs140252141, ESP rs140252141, ExAC rs140252141, TOPMed rs140252141, CADD 27.40, Likely benign
- Y14F (p.Tyr14Phe), gnomAD rs2051891927, CADD 16.60
- V15I (p.Val15Ile), rs146698039, ClinGen CA8609123, cosmic curated COSV99493, ClinVar RCV000996566, CADD 0.20, PolyPhen-2 0.00, Likely benign, not provided; Inborn genetic diseases
- V15L (p.Val15Leu), rs146698039, ClinGen CA8609124, ClinVar RCV003077619, ESP rs146698039, CADD 0.15, PolyPhen-2 0.00, Uncertain significance, not provided
- S16F (p.Ser16Phe), TOPMed rs1292604622
- G18R (p.Gly18Arg), rs1354251613, Ensembl rs1354251613, CADD 9.75, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- G18V (p.Gly18Val), rs2508951149, ClinGen CA399849182, ClinVar RCV004548501, CADD 2.23, PolyPhen-2 0.00, Pathogenic, GFAP-related disorder
- E19K (p.Glu19Lys), NCI-TCGA Cosmic COSV5365, cosmic curated COSV53650, CADD 16.70, PolyPhen-2 0.01, Variant assessed as somatic; moderate impact.
- M20T (p.Met20Thr), Ensembl rs2145643272
- M20V (p.Met20Val), ESP rs371392414, ExAC rs371392414, gnomAD rs371392414
- M21I (p.Met21Ile), rs1266043362, ClinGen CA399849158, ClinVar RCV003703239, gnomAD rs1266043362, CADD 8.27, PolyPhen-2 0.00, Uncertain significance, not provided
- V22G (p.Val22Gly), Ensembl rs1597865100
- G23A (p.Gly23Ala), rs1469741542, ClinGen CA399849146, ClinVar RCV002654093, gnomAD rs1469741542, CADD 13.40, PolyPhen-2 0.02, Uncertain significance, not provided
- G23E (p.Gly23Glu), gnomAD rs1469741542, CADD 15.80, PolyPhen-2 0.03, Uncertain significance
- G23V (p.Gly23Val), gnomAD rs1469741542, CADD 16.20, PolyPhen-2 0.12, Uncertain significance
- G24C (p.Gly24Cys), cosmic curated COSV53654
- G24S (p.Gly24Ser), rs2051890499, ClinGen CA399849144, ClinVar RCV003734474, gnomAD rs2051890499, CADD 6.42, PolyPhen-2 0.00, Uncertain significance, not provided
- G24V (p.Gly24Val), TOPMed rs2051890322, CADD 11.80, PolyPhen-2 0.00
- L25Q (p.Leu25Gln), ESP rs376999852, TOPMed rs376999852, gnomAD rs376999852, CADD 13.20, PolyPhen-2 0.05
- A26D (p.Ala26Asp), 1000Genomes rs139837765, ESP rs139837765, ExAC rs139837765, TOPMed rs139837765, CADD 8.25, PolyPhen-2 0.01, Uncertain significance
- A26G (p.Ala26Gly), 1000Genomes rs139837765, ESP rs139837765, ExAC rs139837765, TOPMed rs139837765, CADD 7.07, PolyPhen-2 0.00, Uncertain significance
- A26P (p.Ala26Pro), TOPMed rs1231379140, gnomAD rs1231379140, CADD 13.30, PolyPhen-2 0.01, Likely benign
- A26T (p.Ala26Thr), rs1231379140, ClinGen CA399849134, ClinVar RCV003419756, TOPMed rs1231379140, CADD 12.60, PolyPhen-2 0.00, Likely benign, not provided
- A26V (p.Ala26Val), rs139837765, ClinGen CA8609113, ClinVar RCV002000806, ClinVar RCV002579654, CADD 7.48, PolyPhen-2 0.00, Uncertain significance, not specified; not provided; Inborn genetic diseases
- G28D (p.Gly28Asp), Ensembl rs2145643134
- G28R (p.Gly28Arg), 1000Genomes rs199848423, CADD 5.25, PolyPhen-2 0.02
- R29C (p.Arg29Cys), rs370903792, ClinGen CA8609112, ClinVar RCV001727038, ClinVar RCV004040002, CADD 23.40, PolyPhen-2 0.33, Uncertain significance, Inborn genetic diseases; not provided
- R29H (p.Arg29His), rs201998644, ClinGen CA8609111, ClinVar RCV002046034, ClinVar RCV004046788, CADD 14.10, PolyPhen-2 0.00, Conflicting interpretations, not provided; Inborn genetic diseases; not specified
- R29L (p.Arg29Leu), cosmic curated COSV53648
- R30C (p.Arg30Cys), rs770249831, ClinGen CA8609110, NCI-TCGA Cosmic COSV5364, cosmic curated COSV53648, CADD 24.70, PolyPhen-2 0.00, Uncertain significance, not provided
- R30H (p.Arg30His), rs373688797, ClinGen CA8609109, cosmic curated COSV53652, ClinVar RCV001997425, CADD 16.20, PolyPhen-2 0.00, Likely benign, Inborn genetic diseases; not provided
- R30P (p.Arg30Pro), ESP rs373688797, ExAC rs373688797, TOPMed rs373688797, gnomAD rs373688797, CADD 17.60, PolyPhen-2 0.09, Likely benign
- P33L (p.Pro33Leu), cosmic curated COSV10502
- G34A (p.Gly34Ala), cosmic curated COSV99493
- T35A (p.Thr35Ala), ExAC rs754484687, gnomAD rs754484687, CADD 2.18, PolyPhen-2 0.00, Uncertain significance
- T35I (p.Thr35Ile), gnomAD rs1376759037, CADD 14.00, PolyPhen-2 0.00
- T35N (p.Thr35Asn), gnomAD rs1376759037, CADD 12.90, PolyPhen-2 0.01
- T35P (p.Thr35Pro), cosmic curated COSV53651, ExAC rs754484687, gnomAD rs754484687, CADD 4.28, PolyPhen-2 0.00, Uncertain significance
- T35S (p.Thr35Ser), rs754484687, ClinGen CA8609106, ClinVar RCV002569617, ExAC rs754484687, CADD 0.32, PolyPhen-2 0.00, Uncertain significance, not provided
- R36C (p.Arg36Cys), rs1236176019, NCI-TCGA Cosmic COSV9949, cosmic curated COSV99493, TOPMed rs1236176019, CADD 27.00, PolyPhen-2 0.54, Variant assessed as somatic; moderate impact.
- R36H (p.Arg36His), rs375709542, ClinGen CA8609102, cosmic curated COSV53650, ClinVar RCV002922899, CADD 24.20, PolyPhen-2 0.47, Uncertain significance, not provided
- R36L (p.Arg36Leu), ESP rs375709542, ExAC rs375709542, TOPMed rs375709542, gnomAD rs375709542, CADD 22.50, PolyPhen-2 0.00, Uncertain significance
- S38F (p.Ser38Phe), rs1455211354, ClinGen CA399849069, NCI-TCGA Cosmic COSV5365, cosmic curated COSV53653, CADD 24.50, PolyPhen-2 0.61, Uncertain significance, not provided
- A40P (p.Ala40Pro), 1000Genomes rs564205924, ExAC rs564205924, gnomAD rs564205924, CADD 17.70, PolyPhen-2 0.00
- R41* (p.Arg41Ter), ExAC rs750178537, TOPMed rs750178537, gnomAD rs750178537, CADD 36.00
- R41L (p.Arg41Leu), NCI-TCGA Cosmic COSV9949, cosmic curated COSV99493, Variant assessed as somatic; moderate impact.
- R41Q (p.Arg41Gln), ExAC rs767435467, TOPMed rs767435467, gnomAD rs767435467, CADD 21.00, PolyPhen-2 0.00
- M42I (p.Met42Ile), gnomAD rs1304504344, CADD 10.40, PolyPhen-2 0.01
- M42K (p.Met42Lys), ExAC rs761756851, gnomAD rs761756851, CADD 18.60, PolyPhen-2 0.02
- M42T (p.Met42Thr), ExAC rs761756851, gnomAD rs761756851, CADD 16.70, PolyPhen-2 0.00
- P43S (p.Pro43Ser), rs368169263, 1000Genomes rs368169263, ExAC rs368169263, TOPMed rs368169263, CADD 6.92, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- P43T (p.Pro43Thr), 1000Genomes rs368169263, ExAC rs368169263, TOPMed rs368169263, gnomAD rs368169263
- P44A (p.Pro44Ala), rs144543354, ClinGen CA8609095, ClinVar RCV002204130, ClinVar RCV003089093, CADD 16.80, PolyPhen-2 0.00, Likely benign, not provided; Inborn genetic diseases
- P44H (p.Pro44His), cosmic curated COSV53652
- P44L (p.Pro44Leu), TOPMed rs1353517133, gnomAD rs1353517133, CADD 19.70, PolyPhen-2 0.00
- P44R (p.Pro44Arg), TOPMed rs1353517133, gnomAD rs1353517133, CADD 17.60, PolyPhen-2 0.00
- P45S (p.Pro45Ser), cosmic curated COSV10805, CADD 15.40, PolyPhen-2 0.01
- L46F (p.Leu46Phe), rs1347539627, ClinGen CA399849027, ClinVar RCV003864421, TOPMed rs1347539627, CADD 22.00, PolyPhen-2 0.43, Uncertain significance, not provided
- L46V (p.Leu46Val), rs1347539627, ClinGen CA399849028, ClinVar RCV001997441, TOPMed rs1347539627, CADD 15.40, PolyPhen-2 0.01, Uncertain significance, not provided
- P47L (p.Pro47Leu), rs57474185, ClinGen CA217146, ClinVar RCV000056852, ClinVar RCV000210687, CADD 21.00, PolyPhen-2 0.02, Benign/Likely benign, Inborn genetic diseases; not specified; Alexander disease
- P47Q (p.Pro47Gln), 1000Genomes rs57474185, ESP rs57474185, ExAC rs57474185, TOPMed rs57474185, CADD 18.70, PolyPhen-2 0.00, Benign
- P47P (p.Pro47Pro), gnomAD 17-44905138-T-A, CADD 5.93
- P47T (p.Pro47Thr), gnomAD 17-44905140-G-T, CADD 2.35
- T48S (p.Thr48Ser), rs2508950342, ClinGen CA399849017, ClinVar RCV003555622, Uncertain significance, not provided
- R49L (p.Arg49Leu), ExAC rs747417926, TOPMed rs747417926, gnomAD rs747417926, CADD 22.40, PolyPhen-2 0.01, Uncertain significance
- R49Q (p.Arg49Gln), rs747417926, ClinGen CA8609090, ClinVar RCV002590936, ExAC rs747417926, CADD 23.70, PolyPhen-2 0.27, Uncertain significance, not provided
- R49W (p.Arg49Trp), rs771283454, ClinGen CA8609091, ClinVar RCV002289285, ClinVar RCV003324015, CADD 25.00, PolyPhen-2 0.88, Uncertain significance, not specified; Alexander disease
- V50G (p.Val50Gly), Ensembl rs1597864720
- V50L (p.Val50Leu), ExAC rs754610136, gnomAD rs754610136, CADD 13.70, PolyPhen-2 0.01, Likely benign, not provided
- V50M (p.Val50Met), ExAC rs754610136, gnomAD rs754610136, CADD 22.40, PolyPhen-2 0.12
- D51N (p.Asp51Asn), rs1475697926, ClinGen CA399849003, ClinVar RCV001752141, gnomAD rs1475697926, AlphaMissense 0.78, MetaLR 0.85, Uncertain significance, not provided
- D51Y (p.Asp51Tyr), gnomAD rs1475697926, AlphaMissense 0.78, MetaLR 0.85, Uncertain significance
- F52C (p.Phe52Cys), ExAC rs748791555, gnomAD rs748791555
- F52L (p.Phe52Leu), Ensembl rs2051886633, CADD 24.80, PolyPhen-2 1.00
- S53A (p.Ser53Ala), rs779437010, ClinGen CA8609086, ClinVar RCV003691167, ExAC rs779437010, CADD 22.50, PolyPhen-2 0.13, Uncertain significance, not provided
- L54Q (p.Leu54Gln), NCI-TCGA Cosmic COSV9949, cosmic curated COSV99493, CADD 24.00, PolyPhen-2 0.84, Uncertain significance, not provided
- L54R (p.Leu54Arg), gnomAD rs1281254784
- A55D (p.Ala55Asp), ExAC rs750371041, TOPMed rs750371041, gnomAD rs750371041
- A55V (p.Ala55Val), ExAC rs750371041, TOPMed rs750371041, gnomAD rs750371041, CADD 21.90, PolyPhen-2 0.26
- G56E (p.Gly56Glu), TOPMed rs1196032125, CADD 16.90, PolyPhen-2 0.00
- G56V (p.Gly56Val), cosmic curated COSV99493
- L58F (p.Leu58Phe), TOPMed rs2051885940, CADD 23.40, PolyPhen-2 0.87
- L58P (p.Leu58Pro), rs2508950096, ClinGen CA399848932, ClinVar RCV003740203, Uncertain significance, not provided
- N59S (p.Asn59Ser), ExAC rs767627754, gnomAD rs767627754, CADD 23.40, PolyPhen-2 0.96, Uncertain significance, Inborn genetic diseases
- A60D (p.Ala60Asp), Ensembl rs886053020
- G61V (p.Gly61Val), gnomAD 17-44905126-AC-A, CADD 7.07
- G61D (p.Gly61Asp), rs2051635220, gnomAD 17-44905127-C-T, CADD 9.30
- G61C (p.Gly61Cys), gnomAD 17-44905128-C-A, CADD 7.90
- G61G (p.Gly61Gly), rs1222013223, gnomAD 17-44905147-A-G, CADD 0.79
- K63Q (p.Lys63Gln), rs60095124, ClinGen CA217150, ClinVar RCV000056854, ClinVar RCV000192096, AlphaMissense 0.19, MetaLR 0.35, not provided, not provided; Alexander disease
- E64D (p.Glu64Asp), cosmic curated COSV99493, CADD 3.29, Uncertain significance, not provided
- E64K (p.Glu64Lys), cosmic curated COSV53650
- E64* (p.Glu64Ter), gnomAD 17-44905137-C-A, CADD 5.95
- T65I (p.Thr65Ile), 1000Genomes rs553164022, ExAC rs553164022, gnomAD rs553164022, CADD 8.49
- T65T (p.Thr65Thr), gnomAD 17-44905144-G-A, CADD 6.91
- T65N (p.Thr65Asn), gnomAD 17-44905145-G-T, CADD 4.98
- R66P (p.Arg66Pro), rs797044569, ClinGen CA16043124, ClinVar RCV000413147, Ensembl rs797044569, AlphaMissense 0.86, MetaLR 0.93, Likely pathogenic, not provided
- R66Q (p.Arg66Gln), rs797044569, ClinGen CA347183, ClinVar RCV000192097, ClinVar RCV001288188, AlphaMissense 0.86, MetaLR 0.93, Conflicting interpretations, not provided; Alexander disease
- R66W (p.Arg66Trp), rs1567778698, ClinGen CA399848839, cosmic curated COSV53649, ClinVar RCV001763457, CADD 28.20, PolyPhen-2 1.00, Conflicting interpretations, Inborn genetic diseases; not provided
- A67G (p.Ala67Gly), rs2508949991, ClinGen CA399848825, ClinVar RCV003555621, Uncertain significance, not provided
- A67S (p.Ala67Ser), rs1364674732, NCI-TCGA Cosmic COSV9949, cosmic curated COSV99493, gnomAD rs1364674732, CADD 16.10, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- S68N (p.Ser68Asn), ExAC rs764324311, gnomAD rs764324311
- S68C (p.Ser68Cys), rs180750421, gnomAD 17-44905130-G-C, CADD 10.20
- S68A (p.Ser68Ala), gnomAD 17-44905131-A-C, CADD 5.45
- E69K (p.Glu69Lys), rs797044570, ClinGen CA347184, ClinVar RCV000192098, ClinVar RCV001200224, AlphaMissense 0.92, MetaLR 0.91, Likely pathogenic, not provided; Alexander disease
- R70L (p.Arg70Leu), cosmic curated COSV99493
- R70Q (p.Arg70Gln), rs267607510, ClinGen CA217152, NCI-TCGA Cosmic COSV9949, cosmic curated COSV99493, CADD 22.90, PolyPhen-2 0.15, Conflicting interpretations, Alexander disease; not provided
- R70W (p.Arg70Trp), rs60343255, ClinGen CA217151, cosmic curated COSV53653, ClinVar RCV000056855, AlphaMissense 0.81, MetaLR 0.79, Pathogenic, not provided; Alexander disease
- A71T (p.Ala71Thr), rs267607522, ClinGen CA217153, cosmic curated COSV53648, ClinVar RCV000056857, AlphaMissense 0.11, MetaLR 0.65, not provided
- E72G (p.Glu72Gly), rs1057518685, ClinGen CA16043694, ClinVar RCV000414950, Ensembl rs1057518685, AlphaMissense 0.66, MetaLR 0.84, Likely pathogenic, Alexander disease
- E72K (p.Glu72Lys), rs267607523, ClinGen CA217155, cosmic curated COSV53653, ClinVar RCV000056858, AlphaMissense 0.63, MetaLR 0.82, not provided, Alexander disease; not provided
- E72Q (p.Glu72Gln), TOPMed rs267607523
- M73I (p.Met73Ile), rs2508949861, ClinGen CA399848755, ClinVar RCV003062100, Likely pathogenic, not provided; Alexander disease
- M73K (p.Met73Lys), rs61060395, ClinGen CA217156, ClinVar RCV000056859, ClinVar RCV000192105, AlphaMissense 0.99, MetaLR 0.84, not provided, not provided; Alexander disease
- M73R (p.Met73Arg), rs61060395, ClinGen CA217157, ClinVar RCV000056860, ClinVar RCV000192104, AlphaMissense 0.99, MetaLR 0.84, not provided, Alexander disease; not provided
- M73T (p.Met73Thr), rs61060395, ClinGen CA347186, ClinVar RCV000192103, UniProt VAR 071524, AlphaMissense 0.99, MetaLR 0.84, Pathogenic, Alexander disease
- M73V (p.Met73Val), rs2145642617, ClinGen CA399848761, ClinVar RCV001527383, Ensembl rs2145642617, AlphaMissense 0.89, MetaLR 0.67, Pathogenic, Alexander disease
- M74I (p.Met74Ile), rs1307573872, ClinGen CA399848739, ClinVar RCV003571827, ClinVar RCV005353206, CADD 19.60, PolyPhen-2 0.01, Uncertain significance, Inborn genetic diseases; not provided
- M74T (p.Met74Thr), rs267607504, ClinGen CA217158, ClinVar RCV000056861, ClinVar RCV000192102, AlphaMissense 0.78, MetaLR 0.60, not provided, not provided; Alexander disease
- E75* (p.Glu75Ter), NCI-TCGA Cosmic COSV9949, cosmic curated COSV99493, Variant assessed as somatic; high impact.
- E75K (p.Glu75Lys), rs2508949834, ClinVar RCV004595172, Uncertain significance, Alexander disease
- L76F (p.Leu76Phe), rs57120761, ClinGen CA217160, ClinVar RCV000017557, ClinVar RCV000056863, AlphaMissense 0.99, MetaLR 0.96, Pathogenic, not provided
- L76I (p.Leu76Ile), Ensembl rs57120761, Pathogenic, in ALXDRD
- L76P (p.Leu76Pro), rs2508949801, ClinGen CA399848715, ClinVar RCV003883277, CADD 5.17, Likely pathogenic, Alexander disease
- L76V (p.Leu76Val), rs57120761, ClinGen CA217159, ClinVar RCV000056862, ClinVar RCV000192106, AlphaMissense 0.99, MetaLR 0.96, not provided, not provided; Alexander disease
- N77D (p.Asn77Asp), rs58732244, ClinGen CA399848709, ClinVar RCV002043282, Ensembl rs58732244, AlphaMissense 0.99, MetaLR 0.96, Uncertain significance, not provided
- N77K (p.Asn77Lys), rs149404477, ClinGen CA399848701, ClinVar RCV003560015, UniProt VAR 071527, Pathogenic, not provided
- N77S (p.Asn77Ser), rs57590980, ClinGen CA217162, ClinVar RCV000056865, ClinVar RCV000192107, AlphaMissense 0.96, MetaLR 0.96, Pathogenic, not provided
- N77Y (p.Asn77Tyr), rs58732244, ClinGen CA217161, ClinVar RCV000017558, ClinVar RCV000056864, AlphaMissense 0.99, MetaLR 0.96, Pathogenic, Alexander disease
- D78E (p.Asp78Glu), rs121909720, ClinGen CA341388, ClinVar RCV000017562, ClinVar RCV003556033, CADD 26.20, PolyPhen-2 0.95, Pathogenic, not provided
- D78N (p.Asp78Asn), rs797044571, ClinGen CA347187, ClinVar RCV000192108, UniProt VAR 071529, AlphaMissense 0.48, MetaLR 0.76, not provided, Alexander disease
- D78Y (p.Asp78Tyr), rs797044571, ClinGen CA399848697, ClinVar RCV003064462, AlphaMissense 0.48, MetaLR 0.76, Pathogenic, not provided
- R79C (p.Arg79Cys), rs59793293, ClinGen CA217166, cosmic curated COSV99493, ClinVar RCV000017554, AlphaMissense 0.91, MetaLR 0.89, Pathogenic, not provided; Alexander disease
- R79G (p.Arg79Gly), rs59793293, ClinGen CA217165, ClinVar RCV000056867, ClinVar RCV000192109, AlphaMissense 0.91, MetaLR 0.89, Pathogenic, not provided
- R79H (p.Arg79His), rs59285727, ClinGen CA217167, cosmic curated COSV53649, ClinVar RCV000017553, AlphaMissense 1.00, MetaLR 0.93, Pathogenic, not provided; Alexander disease
- R79L (p.Arg79Leu), rs59285727, ClinGen CA217169, ClinVar RCV000056871, ClinVar RCV000192112, AlphaMissense 1.00, MetaLR 0.93, Pathogenic, not provided
- R79P (p.Arg79Pro), rs59285727, ClinGen CA217168, ClinVar RCV000056870, ClinVar RCV000192111, AlphaMissense 1.00, MetaLR 0.93, not provided, not provided; Alexander disease
- R79S (p.Arg79Ser), rs59793293, ClinGen CA217163, cosmic curated COSV99493, ClinVar RCV000056866, AlphaMissense 0.91, MetaLR 0.89, Uncertain significance, not provided
- F80S (p.Phe80Ser), rs797044572, ClinGen CA347188, ClinVar RCV000192113, Ensembl rs797044572, AlphaMissense 1.00, MetaLR 0.89, not provided, Alexander disease
- A81D (p.Ala81Asp), rs1597864461, ClinGen CA399848662, ClinVar RCV000789012, Ensembl rs1597864461, AlphaMissense 0.99, MetaLR 0.94, Pathogenic, Alexander disease
- S82C (p.Ser82Cys), Ensembl rs2051883303
- Y83H (p.Tyr83His), rs267607506, ClinGen CA217170, ClinVar RCV000056872, ClinVar RCV000192114, AlphaMissense 0.98, MetaLR 0.93, not provided, not provided; Alexander disease
- Y83N (p.Tyr83Asn), rs267607506, ClinGen CA291034264, ClinVar RCV002508567, TOPMed rs267607506, AlphaMissense 0.98, MetaLR 0.93, Uncertain significance, not provided
- Y83S (p.Tyr83Ser), rs58454592, ClinGen CA217171, ClinVar RCV000056873, Ensembl rs58454592, AlphaMissense 0.97, MetaLR 0.90, not provided
- I84M (p.Ile84Met), rs571151302, ClinGen CA399848618, ClinVar RCV000498900, ClinVar RCV002051858, AlphaMissense 0.79, MetaLR 0.82, Likely pathogenic, Alexander disease; not provided
- I84I (p.Ile84Ile), gnomAD 17-44905120-A-G, CADD 10.40
- I84V (p.Ile84Val), gnomAD 17-44905122-T-C, CADD 8.22
- E85* (p.Glu85Ter), cosmic curated COSV99493
- E85K (p.Glu85Lys), rs907564777, ClinGen CA291034253, NCI-TCGA Cosmic COSV5365, cosmic curated COSV53650, CADD 27.50, PolyPhen-2 0.87, Uncertain significance, not provided
- E85Q (p.Glu85Gln), NCI-TCGA Cosmic COSV5365, NCI-TCGA Cosmic COSV9949, cosmic curated COSV99493, Uncertain significance
- K86E (p.Lys86Glu), rs797044573, ClinGen CA347190, ClinVar RCV000192115, UniProt VAR 071534, AlphaMissense 0.93, MetaLR 0.92, not provided, Alexander disease
- K86R (p.Lys86Arg), rs267607524, ClinGen CA217176, ClinVar RCV000056875, Ensembl rs267607524, AlphaMissense 0.26, MetaLR 0.81, not provided
- V87F (p.Val87Phe), rs267607518, ClinGen CA8609075, ClinVar RCV002042292, ExAC rs267607518, AlphaMissense 0.97, MetaLR 0.93, Conflicting interpretations, not provided
- V87G (p.Val87Gly), rs60449251, ClinGen CA217180, ClinVar RCV000056877, ClinVar RCV000192119, AlphaMissense 0.78, MetaLR 0.94, not provided, not provided; Alexander disease
Public GFAP analysis runs
- GFAP analysis run — GFAP (795 variants) — completed 2026-08-22