FGFR1 (P11362) variants and mutations
FGFR1 (also known as P11362) is a human protein-coding gene encoding a fibroblast growth factor receptor 1 protein. Its fibroblast-growth-factor signaling controls proliferation, differentiation, migration, and developmental patterning in many tissues. Germline pathogenic variants can cause hypogonadotropic hypogonadism or craniosynostosis syndromes, while fusions and other activating alterations drive selected cancers. This analysis covers 3,739 FGFR1 variants and mutations. Of these, 34% have computational variant effect predictions. Disease context includes hypogonadotropic hypogonadism 2 with or without anosmia, Hartsfield-Bixler-Demyer syndrome, and Pfeiffer syndrome. Example FGFR1 variants include W2*, W2C, and W2G.
Variant analysis overview
- Gene: FGFR1
- Protein: P11362
- UniProt accession: P11362
- Organism: Homo sapiens
- Variants analyzed: 3739
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 3,562 unspecified-consequence records; 1 natural variant; 3 stop lost; 84 synonymous variants; 62 missense variants; 11 frameshift variants; 2 stop-gained variants; 4 in-frame deletions; 2 splice-region variants; 1 protein altering variant; 6 substitution
- Prediction scores: 1,280 variants have prediction scores (34% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypogonadotropic hypogonadism 2 with or without anosmia, Hartsfield-Bixler-Demyer syndrome, Pfeiffer syndrome, osteoglophonic dysplasia, hypogonadotropic hypogonadism, encephalocraniocutaneous lipomatosis, cancer, Kallmann syndrome, Jackson-Weiss syndrome, trigonocephaly 1, isolated trigonocephaly, renal cell carcinoma.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 4 domains; 6 binding sites; 15 post-translational modification sites.
- Structural context: 2,647 variants have structural context.
- PTM context: 73 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 FGFR1 variants
Examples include W2*, W2C, W2G, W2R, W2S, S3C, S3I, S3N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- W2* (p.Trp2Ter), Ensembl rs1014244943, Likely pathogenic
- W2C (p.Trp2Cys), Ensembl rs1554594114, cosmic curated COSV10881, Likely pathogenic
- W2G (p.Trp2Gly), Ensembl rs2151347934
- W2R (p.Trp2Arg), Ensembl rs2151347934
- W2S (p.Trp2Ser), Ensembl rs1014244943, MetaLR 0.36, MetaSVM -0.04
- S3C (p.Ser3Cys), gnomAD rs1241452278, REVEL 0.42, CADD 24.30
- S3I (p.Ser3Ile), NCI-TCGA Cosmic COSV5833, cosmic curated COSV58333, Variant assessed as somatic; moderate impact.
- S3N (p.Ser3Asn), rs751651299, ClinGen CA4718958, ClinVar RCV002245098, ClinVar RCV002488624, REVEL 0.22, CADD 22.00, Uncertain significance, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome; not
- S3R (p.Ser3Arg), Ensembl rs2151347523, REVEL 0.38, CADD 24.00
- S3T (p.Ser3Thr), ExAC rs751651299, TOPMed rs751651299, gnomAD rs751651299, MetaLR 0.38, MetaSVM -0.59, Uncertain significance
- W4* (p.Trp4Ter), gnomAD rs760884357, Uncertain significance, in HH2
- W4C (p.Trp4Cys), rs760884357, UniProt VAR 074012, gnomAD rs760884357, cosmic curated COSV10024, REVEL 0.57, CADD 28.50, Uncertain significance, in HH2
- W4L (p.Trp4Leu), Ensembl rs2151347338, Uncertain significance, in HH2
- W4R (p.Trp4Arg), Ensembl rs2151347452, MetaLR 0.55, MetaSVM 0.21, Uncertain significance, in HH2
- W4S (p.Trp4Ser), Ensembl rs2151347338, REVEL 0.55, CADD 23.40, Uncertain significance, in HH2
- K5M (p.Lys5Met), Ensembl rs2151347128
- K5N (p.Lys5Asn), TOPMed rs1833162652
- K5R (p.Lys5Arg), Ensembl rs2151347128
- K5T (p.Lys5Thr), Ensembl rs2151347128, MetaLR 0.31, MetaSVM -0.72
- C6* (p.Cys6Ter), gnomAD rs1240707574
- C6F (p.Cys6Phe), Ensembl rs2151346848, Uncertain significance, Pfeiffer syndrome; Hypogonadotropic hypogonadism 2 with or without anosmia
- C6G (p.Cys6Gly), Ensembl rs2151346966
- C6S (p.Cys6Ser), rs2151346848, ClinGen CA370767262, ClinVar RCV003802617, Ensembl rs2151346848, AlphaMissense 0.09, MetaLR 0.22, Uncertain significance, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome
- C6W (p.Cys6Trp), gnomAD rs1240707574
- C6Y (p.Cys6Tyr), Ensembl rs2151346848, MetaLR 0.24, MetaSVM -0.78, Uncertain significance
- L7F (p.Leu7Phe), gnomAD rs1202687392, REVEL 0.35, CADD 23.90
- L7H (p.Leu7His), 1000Genomes rs532741632, ExAC rs532741632, TOPMed rs532741632, gnomAD rs532741632, REVEL 0.67, CADD 25.10, Uncertain significance
- L7I (p.Leu7Ile), gnomAD rs1202687392
- L7P (p.Leu7Pro), 1000Genomes rs532741632, ExAC rs532741632, TOPMed rs532741632, gnomAD rs532741632, Uncertain significance
- L7R (p.Leu7Arg), rs532741632, ClinGen CA4718957, ClinVar RCV001903731, ClinVar RCV002478336, REVEL 0.62, CADD 25.30, Uncertain significance, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome; not
- L7V (p.Leu7Val), gnomAD rs1202687392
- L8F (p.Leu8Phe), cosmic curated COSV10736, TOPMed rs1259538191, gnomAD rs1259538191, REVEL 0.43, CADD 22.60
- L8I (p.Leu8Ile), TOPMed rs1259538191, gnomAD rs1259538191
- L8P (p.Leu8Pro), Ensembl rs2151346449
- L8V (p.Leu8Val), TOPMed rs1259538191, gnomAD rs1259538191
- F9I (p.Phe9Ile), ExAC rs750602076, TOPMed rs750602076, gnomAD rs750602076, REVEL 0.28, CADD 16.90
- F9L (p.Phe9Leu), TOPMed rs971805245, gnomAD rs971805245, Likely benign
- F9Y (p.Phe9Tyr), Ensembl rs2151346298, MetaLR 0.39, MetaSVM -0.62
- W10* (p.Trp10Ter), Ensembl rs2151346071
- W10C (p.Trp10Cys), NCI-TCGA Cosmic COSV5833, cosmic curated COSV58332, Ensembl rs2151346019, Variant assessed as somatic; moderate impact.
- W10R (p.Trp10Arg), TOPMed rs1285368969, gnomAD rs1285368969, REVEL 0.57, CADD 27.00, Uncertain significance, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome
- W10S (p.Trp10Ser), Ensembl rs2151346071, MetaLR 0.56, MetaSVM 0.01
- A11P (p.Ala11Pro), ExAC rs765703437, gnomAD rs765703437
- A11S (p.Ala11Ser), ExAC rs765703437, gnomAD rs765703437
- A11T (p.Ala11Thr), ExAC rs765703437, gnomAD rs765703437
- A11V (p.Ala11Val), ExAC rs762020019, gnomAD rs762020019, REVEL 0.43, CADD 22.10
- V12L (p.Val12Leu), cosmic curated COSV10588, gnomAD rs1563627828, REVEL 0.34, CADD 21.50
- V12M (p.Val12Met), rs1563627828, gnomAD rs1563627828, REVEL 0.39, CADD 22.60, Variant assessed as somatic; moderate impact.
- L13P (p.Leu13Pro), rs764533580, ClinGen CA4718951, NCI-TCGA Cosmic COSV1002, cosmic curated COSV10024, CADD 3.27, Uncertain significance, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome
- L13Q (p.Leu13Gln), ExAC rs764533580, TOPMed rs764533580, gnomAD rs764533580, MetaLR 0.59, MetaSVM 0.28, Uncertain significance
- L13V (p.Leu13Val), Ensembl rs2151345697, CADD 6.00
- V14A (p.Val14Ala), Ensembl rs2151345357
- V14D (p.Val14Asp), Ensembl rs2151345357
- V14F (p.Val14Phe), Ensembl rs2151345471
- V14G (p.Val14Gly), Ensembl rs2151345357
- V14I (p.Val14Ile), Ensembl rs2151345471
- V14L (p.Val14Leu), Ensembl rs2151345471
- T15A (p.Thr15Ala), Ensembl rs1586746653
- T15I (p.Thr15Ile), TOPMed rs1833149747
- T15P (p.Thr15Pro), Ensembl rs1586746653
- T15R (p.Thr15Arg), TOPMed rs1833149747
- T15S (p.Thr15Ser), Ensembl rs1586746653, MetaLR 0.49, MetaSVM 0.06
- A16D (p.Ala16Asp), ExAC rs200596591, gnomAD rs200596591, Uncertain significance
- A16G (p.Ala16Gly), ExAC rs200596591, gnomAD rs200596591, REVEL 0.44, CADD 24.70, Uncertain significance, FGFR1-related disorder; Hypogonadotropic hypogonadism 2 with or without anosmia
- A16P (p.Ala16Pro), Ensembl rs1833149044
- A16S (p.Ala16Ser), Ensembl rs1833149044
- A16T (p.Ala16Thr), Ensembl rs1833149044, REVEL 0.41, CADD 25.80
- A16V (p.Ala16Val), rs200596591, ClinGen CA4718949, ClinVar RCV004529804, ClinVar RCV006561547, REVEL 0.40, CADD 23.00, Uncertain significance, FGFR1-related disorder; Hypogonadotropic hypogonadism 2 with or without anosmia
- T17A (p.Thr17Ala), Ensembl rs2151344554
- T17I (p.Thr17Ile), Ensembl rs2151344443
- T17P (p.Thr17Pro), Ensembl rs2151344554
- T17R (p.Thr17Arg), Ensembl rs2151344443, MetaLR 0.48, MetaSVM 0.21
- L18F (p.Leu18Phe), ExAC rs771549051, TOPMed rs771549051, gnomAD rs771549051
- L18H (p.Leu18His), Ensembl rs2151344150
- L18V (p.Leu18Val), ExAC rs771549051, TOPMed rs771549051, gnomAD rs771549051
- C19* (p.Cys19Ter), Ensembl rs2151343740
- C19S (p.Cys19Ser), Ensembl rs2151343971, REVEL 0.32, CADD 17.20, Uncertain significance, not provided
- C19W (p.Cys19Trp), Ensembl rs2151343740, REVEL 0.52, CADD 23.80
- C19Y (p.Cys19Tyr), ExAC rs759243486, TOPMed rs759243486, gnomAD rs759243486, REVEL 0.43, CADD 23.20, Uncertain significance
- T20A (p.Thr20Ala), Ensembl rs1563627473, REVEL 0.23, CADD 13.20
- T20I (p.Thr20Ile), NCI-TCGA Cosmic COSV5833, cosmic curated COSV58336, Ensembl rs2151343495, Variant assessed as somatic; moderate impact.
- T20P (p.Thr20Pro), Ensembl rs1563627473, REVEL 0.33, CADD 17.90
- T20S (p.Thr20Ser), Ensembl rs1563627473, MetaLR 0.33, MetaSVM -0.72
- A21D (p.Ala21Asp), Ensembl rs2151343110, CADD 5.13
- A21G (p.Ala21Gly), Ensembl rs2151343110, CADD 6.48
- A21P (p.Ala21Pro), gnomAD rs1383262590, Uncertain significance
- A21S (p.Ala21Ser), gnomAD rs1383262590, CADD 7.51, Uncertain significance
- A21T (p.Ala21Thr), rs1383262590, ClinGen CA370767174, cosmic curated COSV58328, ClinVar RCV001762937, REVEL 0.36, CADD 22.00, Uncertain significance, not provided
- A21V (p.Ala21Val), Ensembl rs2151343110, CADD 6.34
- R22G (p.Arg22Gly), rs148343099, ClinGen CA4718945, ClinVar RCV003801079, ESP rs148343099, REVEL 0.59, CADD 24.40, Uncertain significance, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome
- R22K (p.Arg22Lys), Ensembl rs2151342815
- R22M (p.Arg22Met), Ensembl rs2151342815
- R22S (p.Arg22Ser), rs17175750, UniProt VAR 019290, 1000Genomes rs17175750, ESP rs17175750, REVEL 0.53, CADD 22.40, Conflicting interpretations, not specified; Hypogonadotropic hypogonadism; not provided
- R22T (p.Arg22Thr), Ensembl rs2151342815, REVEL 0.57, CADD 22.60
- R22W (p.Arg22Trp), ESP rs148343099, ExAC rs148343099, TOPMed rs148343099, gnomAD rs148343099, MetaLR 0.53, MetaSVM 0.05, Uncertain significance
- P23A (p.Pro23Ala), Ensembl rs2151342551
- P23L (p.Pro23Leu), rs143341876, ClinGen CA4718943, cosmic curated COSV58345, ClinVar RCV001161821, REVEL 0.54, CADD 25.10, Conflicting interpretations, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome; not
- P23Q (p.Pro23Gln), ESP rs143341876, ExAC rs143341876, TOPMed rs143341876, gnomAD rs143341876, Benign
- P23R (p.Pro23Arg), ESP rs143341876, ExAC rs143341876, TOPMed rs143341876, gnomAD rs143341876, REVEL 0.55, CADD 23.10, Benign
- P23S (p.Pro23Ser), cosmic curated COSV58338, Ensembl rs2151342551
- P23T (p.Pro23Thr), Ensembl rs2151342551
- S24A (p.Ser24Ala), Ensembl rs2151342326
- S24C (p.Ser24Cys), Ensembl rs2151342246
- S24F (p.Ser24Phe), cosmic curated COSV58342, Ensembl rs2151342246
- S24P (p.Ser24Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S24T (p.Ser24Thr), Ensembl rs2151342326
- S24Y (p.Ser24Tyr), Ensembl rs2151342246, MetaLR 0.44, MetaSVM -0.37
- P25A (p.Pro25Ala), Ensembl rs1833137533, REVEL 0.24, CADD 18.40
- P25L (p.Pro25Leu), rs149206728, ClinGen CA175774442, cosmic curated COSV58328, NCI-TCGA Cosmic COSV5834, REVEL 0.24, CADD 19.90, Uncertain significance, not provided; FGFR1-related disorder
- P25Q (p.Pro25Gln), cosmic curated COSV58342, ESP rs149206728, TOPMed rs149206728, gnomAD rs149206728, Uncertain significance
- P25R (p.Pro25Arg), ESP rs149206728, TOPMed rs149206728, gnomAD rs149206728, Uncertain significance
- P25S (p.Pro25Ser), cosmic curated COSV58329, Ensembl rs1833137533, MetaLR 0.41, MetaSVM -0.39
- P25T (p.Pro25Thr), Ensembl rs1833137533, REVEL 0.29, CADD 19.80, Uncertain significance, not provided
- T26A (p.Thr26Ala), Ensembl rs2151341737
- T26I (p.Thr26Ile), TOPMed rs1833133571, Uncertain significance
- T26N (p.Thr26Asn), rs1833133571, ClinGen CA370767146, ClinVar RCV002036465, TOPMed rs1833133571, AlphaMissense 0.09, MetaLR 0.53, Uncertain significance, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome
- T26P (p.Thr26Pro), Ensembl rs2151341737
- T26S (p.Thr26Ser), Ensembl rs2151341737, MetaLR 0.40, MetaSVM -0.42, Uncertain significance
- L27* (p.Leu27Ter), Ensembl rs2151341409
- L27F (p.Leu27Phe), rs1230569367, TOPMed rs1230569367, gnomAD rs1230569367, ClinGen CA370767137, REVEL 0.34, CADD 22.70, Uncertain significance, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome
- L27M (p.Leu27Met), Ensembl rs2151341483
- L27S (p.Leu27Ser), Ensembl rs2151341409
- P28A (p.Pro28Ala), TOPMed rs1204612499, gnomAD rs1204612499, REVEL 0.29, CADD 15.50, Uncertain significance
- P28H (p.Pro28His), ESP rs145434725, ExAC rs145434725, TOPMed rs145434725, gnomAD rs145434725, Pathogenic
- P28L (p.Pro28Leu), rs145434725, ClinGen CA4718940, ClinVar RCV000493590, ClinVar RCV001856982, REVEL 0.37, CADD 23.00, Conflicting interpretations, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome; Hart
- P28R (p.Pro28Arg), ESP rs145434725, ExAC rs145434725, TOPMed rs145434725, gnomAD rs145434725, MetaLR 0.61, MetaSVM 0.20, Pathogenic
- P28S (p.Pro28Ser), rs1204612499, ClinGen CA370767134, ClinVar RCV003789215, TOPMed rs1204612499, REVEL 0.32, CADD 16.90, Uncertain significance, Pfeiffer syndrome; Hypogonadotropic hypogonadism 2 with or without anosmia
- E29A (p.Glu29Ala), ExAC rs758551875, TOPMed rs758551875, gnomAD rs758551875, REVEL 0.39, CADD 22.60
- E29D (p.Glu29Asp), gnomAD rs1240973335, REVEL 0.28, CADD 16.70
- E29G (p.Glu29Gly), ExAC rs758551875, TOPMed rs758551875, gnomAD rs758551875, REVEL 0.46, CADD 22.90
- E29K (p.Glu29Lys), Ensembl rs2151340978
- E29Q (p.Glu29Gln), Ensembl rs2151340978
- E29V (p.Glu29Val), ExAC rs758551875, TOPMed rs758551875, gnomAD rs758551875, MetaLR 0.59, MetaSVM -0.26
- Q30H (p.Gln30His), Ensembl rs2151340680
- Q30K (p.Gln30Lys), Ensembl rs2151340774
- A31D (p.Ala31Asp), Ensembl rs2150967605, REVEL 0.32, CADD 23.80
- A31G (p.Ala31Gly), Ensembl rs2150967605
- A31P (p.Ala31Pro), Ensembl rs2151340565
- A31S (p.Ala31Ser), cosmic curated COSV10024, Ensembl rs2151340565
- A31T (p.Ala31Thr), Ensembl rs2151340565
- A31V (p.Ala31Val), Ensembl rs2150967605, REVEL 0.22, CADD 21.70
- Q32* (p.Gln32Ter), cosmic curated COSV10642, Ensembl rs2150967516
- Q32E (p.Gln32Glu), Ensembl rs2150967516
- Q32H (p.Gln32His), Ensembl rs2150967402
- Q32L (p.Gln32Leu), Ensembl rs2150967455
- Q32P (p.Gln32Pro), Ensembl rs2150967455
- Q32R (p.Gln32Arg), Ensembl rs2150967455
- P33H (p.Pro33His), Ensembl rs2150967303
- P33L (p.Pro33Leu), cosmic curated COSV58343, Ensembl rs2150967303, REVEL 0.41, CADD 23.60
- P33R (p.Pro33Arg), Ensembl rs2150967303
- P33S (p.Pro33Ser), TOPMed rs1371683958, gnomAD rs1371683958, REVEL 0.19, AlphaMissense 0.07
- P33T (p.Pro33Thr), rs1371683958, ClinGen CA370736658, ClinVar RCV003147252, AlphaMissense 0.07, MetaLR 0.32, Uncertain significance, not provided
- W34* (p.Trp34Ter), rs2150967174, ClinGen CA370736649, ClinVar RCV003312714, AlphaMissense 0.07, MetaLR 0.21, Pathogenic
- W34C (p.Trp34Cys), Ensembl rs2150967117, REVEL 0.37, CADD 23.20
- W34L (p.Trp34Leu), Ensembl rs2150967174
- W34R (p.Trp34Arg), Ensembl rs2150967212, REVEL 0.35, CADD 22.60
- W34S (p.Trp34Ser), Ensembl rs2150967174, SIFT 0.58
- G35* (p.Gly35Ter), ExAC rs773442656, TOPMed rs773442656, gnomAD rs773442656, CADD 36.00
- G35A (p.Gly35Ala), Ensembl rs2150967003, SIFT 0.44
- G35E (p.Gly35Glu), NCI-TCGA TCGA novel, Ensembl rs2150967003, REVEL 0.29, CADD 20.70, Variant assessed as somatic; high impact.
- G35R (p.Gly35Arg), ExAC rs773442656, TOPMed rs773442656, gnomAD rs773442656, REVEL 0.28, CADD 22.60
- A36G (p.Ala36Gly), gnomAD rs1424869652
- A36S (p.Ala36Ser), Ensembl rs2150966948, Uncertain significance
- A36T (p.Ala36Thr), rs2150966948, ClinGen CA370736636, ClinVar RCV001974287, Ensembl rs2150966948, AlphaMissense 0.07, MetaLR 0.22, Uncertain significance, Pfeiffer syndrome; Hypogonadotropic hypogonadism 2 with or without anosmia
- A36V (p.Ala36Val), gnomAD rs1424869652, REVEL 0.21, CADD 19.80
- P37A (p.Pro37Ala), Ensembl rs2150966795
- P37L (p.Pro37Leu), Ensembl rs2150966752
- P37R (p.Pro37Arg), Ensembl rs2150966752
- P37S (p.Pro37Ser), cosmic curated COSV58332, Ensembl rs2150966795
- P37T (p.Pro37Thr), Ensembl rs2150966795
- V38A (p.Val38Ala), Ensembl rs2150966646
- V38E (p.Val38Glu), Ensembl rs2150966646
- V38G (p.Val38Gly), Ensembl rs2150966646, SIFT 0.00
- V38L (p.Val38Leu), ESP rs377555354, ExAC rs377555354, TOPMed rs377555354, gnomAD rs377555354, REVEL 0.11, CADD 19.50, Likely benign
- V38M (p.Val38Met), rs377555354, ClinGen CA4718877, ClinVar RCV003788141, ClinVar RCV005040499, REVEL 0.15, CADD 21.40, Conflicting interpretations, Hypogonadotropic hypogonadism 2 with or without anosmia; Pfeiffer syndrome; Ence
- E39* (p.Glu39Ter), gnomAD rs1164001578
- E39D (p.Glu39Asp), Ensembl rs2150966392
- E39G (p.Glu39Gly), TOPMed rs1822338280, REVEL 0.43, CADD 24.20
- E39K (p.Glu39Lys), gnomAD rs1164001578, REVEL 0.28, CADD 22.80
- E39Q (p.Glu39Gln), gnomAD rs1164001578, SIFT 0.13
Public FGFR1 analysis runs
- FGFR1 analysis run — FGFR1 (3,739 variants) — completed 2026-08-18