FMR1 (Q06787) variants and mutations
FMR1 (also known as Q06787) is a human protein-coding gene encoding a fragile X messenger ribonucleoprotein 1 protein. Its FMRP product binds neuronal RNAs and regulates their transport and local translation at synapses. Full CGG-repeat expansion silences the gene and causes fragile X syndrome, while premutation alleles can cause tremor-ataxia syndrome or primary ovarian insufficiency. This analysis covers 608 FMR1 variants and mutations. Of these, 60% have computational variant effect predictions. Disease context includes fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and premature ovarian failure 1. Example FMR1 variants include E2K, E2*, and E2G.
Variant analysis overview
- Gene: FMR1
- Protein: Q06787
- UniProt accession: Q06787
- Organism: Homo sapiens
- Variants analyzed: 608
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 482 unspecified-consequence records; 8 stop-gained variants; 84 missense variants; 26 synonymous variants; 4 splice-region variants; 2 frameshift variants; 2 substitution
- Prediction scores: 365 variants have prediction scores (60% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: fragile X syndrome, fragile X-associated tremor/ataxia syndrome, premature ovarian failure 1, Intellectual disability, hereditary disease, type 2 diabetes mellitus, Autistic behavior, adolescent idiopathic scoliosis, femur fracture, autism, Neurodevelopmental abnormality, cancer.
Protein structure and variant hotspots
- Protein features: 4 domains; 27 post-translational modification sites.
- Structural context: 212 variants have structural context.
- PTM context: 25 variants overlap post-translational modification sites.
- Experimental data: 66 protein positions have experimental scores. Source: FMR1 K Homology domain, type 1 domainome 1.0.
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 FMR1 variants
Examples include E2K, E2*, E2G, E2E, E3D, E3*, E3G, E3E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2K (p.Glu2Lys), Ensembl rs2042610275
- E2* (p.Glu2Ter), gnomAD X-147912183-G-T, CADD 38.00
- E2G (p.Glu2Gly), gnomAD X-147912184-A-G, REVEL 0.14, CADD 32.00
- E2E (p.Glu2Glu), gnomAD X-147912185-G-A, CADD 14.30
- E3D (p.Glu3Asp), gnomAD rs1557173986, REVEL 0.12, CADD 18.50
- E3* (p.Glu3Ter), gnomAD X-147912186-G-T, CADD 37.00
- E3G (p.Glu3Gly), gnomAD X-147912187-A-G, REVEL 0.07, CADD 26.40
- E3E (p.Glu3Glu), gnomAD X-147912188-G-A, CADD 14.20
- L4L (p.Leu4Leu), gnomAD X-147912189-C-T, CADD 15.50
- L4M (p.Leu4Met), gnomAD X-147912189-C-A, REVEL 0.17, CADD 25.80
- L4P (p.Leu4Pro), gnomAD X-147912190-T-C, REVEL 0.44, CADD 28.90
- L4R (p.Leu4Arg), gnomAD X-147912190-T-G, REVEL 0.27, CADD 32.00
- L4F (p.Leu4Phe), gnomAD X-147912746-C-T, CADD 18.50
- V5E (p.Val5Glu), TOPMed rs1557173996, gnomAD rs1557173996, REVEL 0.28, CADD 22.40
- V5L (p.Val5Leu), ExAC rs781928912, gnomAD rs781928912, REVEL 0.15, CADD 22.30
- V5A (p.Val5Ala), gnomAD X-147912193-T-C, REVEL 0.14, CADD 17.90
- V5V (p.Val5Val), gnomAD X-147912194-G-A, CADD 15.90
- V6A (p.Val6Ala), gnomAD rs1557173998, REVEL 0.34, CADD 26.20
- V6M (p.Val6Met), gnomAD X-147912195-G-A, REVEL 0.29, CADD 26.50
- V6L (p.Val6Leu), gnomAD X-147912195-G-T, REVEL 0.35, CADD 23.60
- V6V (p.Val6Val), rs111485627, gnomAD X-147912197-G-T, CADD 14.10
- E7* (p.Glu7Ter), gnomAD rs1557174005, CADD 39.00
- E7Q (p.Glu7Gln), gnomAD X-147912198-G-C, REVEL 0.40, CADD 25.80
- E7G (p.Glu7Gly), gnomAD X-147912199-A-G, REVEL 0.55, CADD 33.00
- V8M (p.Val8Met), rs1557174007, gnomAD rs1557174007, REVEL 0.34, CADD 26.70, Variant assessed as somatic; moderate impact.
- V8V (p.Val8Val), gnomAD X-147912203-G-A, CADD 14.10
- R9W (p.Arg9Trp), gnomAD X-147912204-C-T, REVEL 0.32, CADD 29.80
- R9R (p.Arg9Arg), gnomAD X-147912204-C-A, CADD 15.40
- R9G (p.Arg9Gly), gnomAD X-147912204-C-G, REVEL 0.32, CADD 32.00
- R9Q (p.Arg9Gln), gnomAD X-147912205-G-A, REVEL 0.23, CADD 24.70
- R9L (p.Arg9Leu), gnomAD X-147912205-G-T, REVEL 0.31, CADD 23.10
- G10V (p.Gly10Val), cosmic curated COSV10587, gnomAD rs1557174013, REVEL 0.36, CADD 26.10
- G10C (p.Gly10Cys), gnomAD X-147912207-G-T, REVEL 0.42, CADD 27.90
- G10D (p.Gly10Asp), gnomAD X-147912208-G-A, REVEL 0.33, CADD 26.00
- G10G (p.Gly10Gly), gnomAD X-147912209-C-A, CADD 13.80
- S11P (p.Ser11Pro), gnomAD X-147912210-T-C, REVEL 0.22, CADD 24.30
- S11T (p.Ser11Thr), gnomAD X-147912210-T-A, REVEL 0.11, CADD 20.60
- S11Y (p.Ser11Tyr), gnomAD X-147912211-C-A, REVEL 0.15, CADD 24.00
- S11F (p.Ser11Phe), gnomAD X-147912211-C-T, REVEL 0.17, CADD 24.40
- S11S (p.Ser11Ser), gnomAD X-147912212-C-T, CADD 15.90
- N12K (p.Asn12Lys), gnomAD X-147912215-T-A, REVEL 0.08, CADD 23.80
- N12N (p.Asn12Asn), rs371928026, gnomAD X-147912215-T-C, CADD 14.80
- G13S (p.Gly13Ser), gnomAD X-147912216-G-A, REVEL 0.53, CADD 32.00
- G13D (p.Gly13Asp), gnomAD X-147912217-G-A, REVEL 0.56, CADD 24.30
- G13G (p.Gly13Gly), gnomAD X-147912218-C-T, CADD 15.40
- G13R (p.Gly13Arg), rs1235932672, gnomAD X-147912740-G-A, CADD 18.40
- G13E (p.Gly13Glu), rs1206971095, gnomAD X-147912741-G-A, CADD 18.60
- G13V (p.Gly13Val), gnomAD X-147912759-G-T, CADD 9.81
- G13W (p.Gly13Trp), gnomAD X-147912764-G-T, CADD 15.30
- A14S (p.Ala14Ser), gnomAD X-147912219-G-T, REVEL 0.20, CADD 24.40
- A14T (p.Ala14Thr), gnomAD X-147912219-G-A, REVEL 0.20, CADD 25.10
- F15F (p.Phe15Phe), gnomAD X-147912224-C-T, CADD 17.20
- Y16C (p.Tyr16Cys), Ensembl rs2042611400
- Y16H (p.Tyr16His), gnomAD X-147912225-T-C, REVEL 0.35, CADD 24.60
- Y16Y (p.Tyr16Tyr), rs1557174018, gnomAD X-147912227-C-T, CADD 16.80
- Y16* (p.Tyr16Ter), gnomAD X-147912227-C-A, CADD 36.00
- K17R (p.Lys17Arg), gnomAD X-147912229-A-G, REVEL 0.17, CADD 31.00
- K17M (p.Lys17Met), gnomAD X-147912229-A-T, REVEL 0.24, CADD 33.00
- K17K (p.Lys17Lys), gnomAD X-147912230-G-A, CADD 26.00
- K17N (p.Lys17Asn), gnomAD X-147912230-G-T, REVEL 0.13, CADD 34.00
- A18=, NCI-TCGA Cosmic COSV9950, Variant assessed as somatic; low impact.
- A18T (p.Ala18Thr), gnomAD X-147921933-G-A, REVEL 0.33, CADD 32.00
- A18E (p.Ala18Glu), gnomAD X-147921934-C-A, REVEL 0.33, CADD 26.60
- A18V (p.Ala18Val), gnomAD X-147921934-C-T, REVEL 0.26, CADD 28.70
- A18A (p.Ala18Ala), gnomAD X-147921935-A-G, CADD 12.20
- F19L (p.Phe19Leu), gnomAD X-147912737-T-C, CADD 20.30
- F19F (p.Phe19Phe), gnomAD X-147912739-C-T, CADD 10.40
- F19S (p.Phe19Ser), gnomAD X-147921937-T-C, REVEL 0.35, CADD 26.90
- V20I (p.Val20Ile), gnomAD X-147921939-G-A, REVEL 0.07, CADD 21.30
- V20E (p.Val20Glu), gnomAD X-147921940-T-A, REVEL 0.68, CADD 26.80
- V20A (p.Val20Ala), gnomAD X-147921940-T-C, REVEL 0.40, CADD 25.90
- K21N (p.Lys21Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K21R (p.Lys21Arg), gnomAD X-147921940-TA-T, CADD 23.90
- K21E (p.Lys21Glu), gnomAD X-147921942-A-G, REVEL 0.42, CADD 25.70
- K21* (p.Lys21Ter), gnomAD X-147921942-A-T, CADD 38.00
- K21M (p.Lys21Met), gnomAD X-147921943-A-T, REVEL 0.46, CADD 26.80
- D22E (p.Asp22Glu), rs2521189826, ClinGen CA414434420, ClinVar RCV002308780, Uncertain significance, not provided
- D22N (p.Asp22Asn), gnomAD X-147921945-G-A, REVEL 0.43, CADD 25.40
- D22G (p.Asp22Gly), gnomAD X-147921946-A-G, REVEL 0.68, CADD 26.90
- D22D (p.Asp22Asp), gnomAD X-147921947-T-C, CADD 10.30
- V23I (p.Val23Ile), NCI-TCGA Cosmic COSV9950, cosmic curated COSV99503, REVEL 0.13, CADD 22.20, Variant assessed as somatic; moderate impact.
- V23D (p.Val23Asp), gnomAD X-147921949-T-A, REVEL 0.74, CADD 27.60
- V23A (p.Val23Ala), gnomAD X-147921949-T-C, REVEL 0.42, CADD 26.50
- V23V (p.Val23Val), rs782201022, gnomAD X-147921950-T-C, CADD 10.60
- H24N (p.His24Asn), NCI-TCGA TCGA novel, REVEL 0.39, CADD 25.80, Variant assessed as somatic; moderate impact.
- H24R (p.His24Arg), rs2124471879, ClinGen CA414434444, ClinVar RCV001758301, Ensembl rs2124471879, REVEL 0.45, CADD 23.50, Uncertain significance, not provided
- H24H (p.His24His), rs997885857, gnomAD X-147912730-T-C, CADD 13.30
- H24Y (p.His24Tyr), gnomAD X-147921951-C-T, REVEL 0.19, CADD 23.80
- E25G (p.Glu25Gly), gnomAD X-147912744-A-G, CADD 17.30
- E25E (p.Glu25Glu), gnomAD X-147912745-G-A, CADD 18.80
- E25* (p.Glu25Ter), gnomAD X-147921954-G-T, CADD 41.00
- E25D (p.Glu25Asp), gnomAD X-147921956-A-T, REVEL 0.10, CADD 15.30
- D26N (p.Asp26Asn), gnomAD X-147921957-G-A, REVEL 0.18, CADD 23.70
- D26V (p.Asp26Val), gnomAD X-147921958-A-T, REVEL 0.35, CADD 26.80
- D26G (p.Asp26Gly), gnomAD X-147921958-A-G, REVEL 0.18, CADD 22.90
- D26D (p.Asp26Asp), gnomAD X-147921959-T-C, CADD 9.23
- S27* (p.Ser27Ter), rs1569545382, ClinGen CA414434492, ClinVar RCV000022880, Ensembl rs1569545382, CADD 37.00, Pathogenic
- S27F (p.Ser27Phe), rs2042656553, gnomAD X-147912756-C-T, CADD 12.30
- S27S (p.Ser27Ser), gnomAD X-147912757-T-C, CADD 5.21
- S27P (p.Ser27Pro), gnomAD X-147921960-T-C, REVEL 0.25, CADD 25.90
- S27L (p.Ser27Leu), gnomAD X-147921961-C-T, REVEL 0.28, CADD 28.10
- I28M (p.Ile28Met), NCI-TCGA Cosmic COSV9950, cosmic curated COSV99503, TOPMed rs2043190133, Variant assessed as somatic; moderate impact.
- I28V (p.Ile28Val), Ensembl rs2043190030, REVEL 0.09, CADD 15.60
- I28T (p.Ile28Thr), gnomAD X-147921964-T-C, REVEL 0.40, CADD 23.60
- T29S (p.Thr29Ser), gnomAD X-147921966-A-T, REVEL 0.45, CADD 22.10
- T29A (p.Thr29Ala), gnomAD X-147921966-A-G, REVEL 0.41, CADD 22.80
- T29I (p.Thr29Ile), gnomAD X-147921967-C-T, REVEL 0.36, CADD 27.30
- T29K (p.Thr29Lys), gnomAD X-147921967-C-A, REVEL 0.43, CADD 25.20
- T29T (p.Thr29Thr), gnomAD X-147921968-A-G, CADD 10.80
- V30I (p.Val30Ile), gnomAD X-147921969-G-A, REVEL 0.18, CADD 21.80
- V30A (p.Val30Ala), gnomAD X-147921970-T-C, REVEL 0.47, CADD 26.20
- V30V (p.Val30Val), gnomAD X-147921971-T-C, CADD 8.92
- A31T (p.Ala31Thr), NCI-TCGA Cosmic COSV9950, cosmic curated COSV99503, REVEL 0.05, CADD 22.40, Variant assessed as somatic; moderate impact.
- A31E (p.Ala31Glu), gnomAD X-147921973-C-A, REVEL 0.12, CADD 24.40
- A31G (p.Ala31Gly), gnomAD X-147921973-C-G, REVEL 0.08, CADD 23.20
- A31V (p.Ala31Val), gnomAD X-147921973-C-T, REVEL 0.12, CADD 22.30
- A31A (p.Ala31Ala), rs1470569372, gnomAD X-147921974-A-G, CADD 11.40
- F32L (p.Phe32Leu), gnomAD X-147921975-T-C, REVEL 0.53, CADD 25.90
- F32S (p.Phe32Ser), gnomAD X-147921976-T-C, REVEL 0.68, CADD 27.80
- F32F (p.Phe32Phe), rs1429282550, gnomAD X-147921977-T-C, CADD 12.60
- E33K (p.Glu33Lys), gnomAD X-147921978-G-A, REVEL 0.56, CADD 29.70
- E33G (p.Glu33Gly), gnomAD X-147921979-A-G, REVEL 0.49, CADD 24.00
- E33E (p.Glu33Glu), gnomAD X-147921980-A-G, CADD 10.10
- N34K (p.Asn34Lys), ExAC rs782350674, TOPMed rs782350674, gnomAD rs782350674, REVEL 0.24, CADD 25.60, Uncertain significance, Inborn genetic diseases
- N34S (p.Asn34Ser), rs1170279830, ClinGen CA414434582, ClinVar RCV001754884, ClinVar RCV004980648, REVEL 0.31, CADD 23.00, Uncertain significance, Inborn genetic diseases; not provided
- N34D (p.Asn34Asp), gnomAD X-147921981-A-G, REVEL 0.28, CADD 22.50
- N35D (p.Asn35Asp), gnomAD X-147921984-A-G, REVEL 0.14, CADD 23.30
- N35S (p.Asn35Ser), gnomAD X-147921985-A-G, REVEL 0.18, CADD 20.30
- N35N (p.Asn35Asn), gnomAD X-147925540-C-T, CADD 14.20
- N35K (p.Asn35Lys), gnomAD X-147925540-C-A, REVEL 0.13, CADD 20.50
- W36G (p.Trp36Gly), rs1482972459, gnomAD X-147912731-T-G, CADD 7.36
- W36* (p.Trp36Ter), gnomAD X-147912732-G-A, CADD 16.50
- W36R (p.Trp36Arg), gnomAD X-147925541-T-C, REVEL 0.56, CADD 27.70
- Q37K (p.Gln37Lys), gnomAD X-147925544-C-A, REVEL 0.27, CADD 22.70
- Q37* (p.Gln37Ter), gnomAD X-147925544-C-T, CADD 37.00
- Q37R (p.Gln37Arg), gnomAD X-147925545-A-G, REVEL 0.42, CADD 23.20
- Q37Q (p.Gln37Gln), gnomAD X-147925546-G-A, CADD 7.05
- P38A (p.Pro38Ala), NCI-TCGA Cosmic COSV5442, cosmic curated COSV54425, NCI-TCGA Cosmic COSV9950, Variant assessed as somatic; moderate impact.
- P38T (p.Pro38Thr), NCI-TCGA Cosmic COSV5442, NCI-TCGA Cosmic COSV9950, cosmic curated COSV99503, REVEL 0.21, CADD 22.40, Variant assessed as somatic; moderate impact.
- P38S (p.Pro38Ser), gnomAD X-147925547-C-T, REVEL 0.20, CADD 20.90
- P38H (p.Pro38His), gnomAD X-147925548-C-A, REVEL 0.28, CADD 24.80
- R40E (p.Arg40Glu), gnomAD X-147912757-TG-T, CADD 9.84
- R40R (p.Arg40Arg), gnomAD X-147912761-C-A, CADD 12.70
- R40* (p.Arg40Ter), gnomAD X-147912761-C-T, CADD 13.20
- R40G (p.Arg40Gly), gnomAD X-147912761-C-G, CADD 12.80
- R40Q (p.Arg40Gln), gnomAD X-147912762-G-A, CADD 6.16
- R40P (p.Arg40Pro), gnomAD X-147912762-G-C, CADD 5.76
- P43T (p.Pro43Thr), NCI-TCGA Cosmic COSV5442, REVEL 0.31, CADD 22.40, Variant assessed as somatic; moderate impact.
- D46V (p.Asp46Val), Ensembl rs2124491380
- F49S (p.Phe49Ser), NCI-TCGA Cosmic COSV9950, cosmic curated COSV99503, Variant assessed as somatic; moderate impact.
- P51H (p.Pro51His), TOPMed rs1473910950, gnomAD rs1473910950, REVEL 0.53, CADD 24.70
- P51L (p.Pro51Leu), TOPMed rs1473910950, gnomAD rs1473910950, REVEL 0.41, CADD 22.10
- P52L (p.Pro52Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P52S (p.Pro52Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V53I (p.Val53Ile), NCI-TCGA TCGA novel, REVEL 0.05, CADD 18.20, Variant assessed as somatic; high impact.
- V53L (p.Val53Leu), ExAC rs782602321, TOPMed rs782602321, gnomAD rs782602321, REVEL 0.05, CADD 18.10
- G54C (p.Gly54Cys), NCI-TCGA Cosmic COSV9950, cosmic curated COSV99503, Variant assessed as somatic; moderate impact.
- N56K (p.Asn56Lys), Ensembl rs2043357807
- D58E (p.Asp58Glu), Ensembl rs2043357885
- D58Y (p.Asp58Tyr), NCI-TCGA Cosmic COSV9950, cosmic curated COSV99503, Variant assessed as somatic; moderate impact.
- I59L (p.Ile59Leu), NCI-TCGA Cosmic COSV5442, cosmic curated COSV54427, REVEL 0.17, CADD 21.00, Variant assessed as somatic; moderate impact.
- D63G (p.Asp63Gly), rs782202548, ClinGen CA10536069, ClinVar RCV002273365, ClinVar RCV005930203, REVEL 0.33, CADD 24.30, Uncertain significance, not provided
- E64K (p.Glu64Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V65F (p.Val65Phe), ExAC rs782438699
- E66D (p.Glu66Asp), ExAC rs782393400
- E66G (p.Glu66Gly), ExAC rs782284934, REVEL 0.77, CADD 33.00
- V67=, NCI-TCGA Cosmic COSV5442, Variant assessed as somatic; low impact.
- Y68F (p.Tyr68Phe), Ensembl rs201498256, REVEL 0.15, CADD 20.90
- N72T (p.Asn72Thr), NCI-TCGA Cosmic COSV9950, cosmic curated COSV99503, Variant assessed as somatic; moderate impact.
- E75Q (p.Glu75Gln), NCI-TCGA Cosmic COSV9950, cosmic curated COSV99503, Variant assessed as somatic; moderate impact.
- E75S (p.Glu75Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- C78G (p.Cys78Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- W80L (p.Trp80Leu), Ensembl rs1557177905
- L81* (p.Leu81Ter), Ensembl rs868907697
- R85G (p.Arg85Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M86T (p.Met86Thr), Ensembl rs1557177916
- G89D (p.Gly89Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F91S (p.Phe91Ser), rs2124505038, ClinGen CA414436085, ClinVar RCV001786130, Ensembl rs2124505038, AlphaMissense 1.00, MetaLR 0.40, Uncertain significance, not provided
- E95* (p.Glu95Ter), NCI-TCGA Cosmic COSV5442, Variant assessed as somatic; high impact.
- E95K (p.Glu95Lys), NCI-TCGA Cosmic COSV5442, cosmic curated COSV54422, Variant assessed as somatic; moderate impact.
Public FMR1 analysis runs
- FMR1 analysis run — FMR1 (608 variants) — completed 2026-08-18