FGFR2 (P21802) variants and mutations

FGFR2 (also known as P21802) is a human protein-coding gene encoding a fibroblast growth factor receptor 2 protein. Its fibroblast-growth-factor signaling regulates proliferation, differentiation, and developmental patterning across multiple tissues. Germline activating variants cause several craniosynostosis syndromes, while somatic mutations, amplification, or fusions can drive cancer. This analysis covers 3,663 FGFR2 variants and mutations. Of these, 4.8% have pathogenic or likely pathogenic clinical classifications, 25% have computational variant effect predictions from REVEL and MutPred, and 22% have population-specific frequency data. Disease context includes Crouzon syndrome, Pfeiffer syndrome, and Apert syndrome. Example FGFR2 variants include M1?, M1V, and V2I.

Variant analysis overview

Gene: FGFR2
Protein: P21802
UniProt accession: P21802
Organism: Homo sapiens
Variants analyzed: 3663
Variant scope: all variants
Completed: 2026-08-10

Variant and mutation evidence

Variant composition: 3,533 unspecified-consequence records; 2 stop retained variant; 5 stop lost; 52 synonymous variants; 48 missense variants; 4 stop-gained variants; 7 frameshift variants; 3 in-frame deletions; 2 splice-region variants; 1 protein altering variant; 6 substitution
Clinical classifications: 177 pathogenic or likely pathogenic; 88 benign or likely benign; 538 uncertain-significance; 1 conflicting; 159 other clinical labels.
Computational signals: 161 REVEL high-risk; 58 MutPred high-risk.
Variant classes: 3,413 missense; 52 synonymous; 187 truncating or splice.
Prediction scores: 924 variants have prediction scores (25% of the analyzed set).
Literature: 62 publications are represented in the literature summary.

Clinical, disease, and population context

Clinical evidence: 61 records have expert-only or criteria-backed evidence.
Clinical annotations: 968 variants have clinical annotations.
Population evidence: 848 variants have population-frequency evidence.
Disease context: 25 disease associations are represented. Top associations: Crouzon syndrome, Pfeiffer syndrome, Apert syndrome, Beare-Stevenson cutis gyrata syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis, Lacrimoauriculodentodigital syndrome, bent bone dysplasia syndrome 1, LADD syndrome 1, Saethre-Chotzen syndrome, familial scaphocephaly syndrome, McGillivray type, LADD syndrome.

Protein structure and variant hotspots

Protein features: 1 transmembrane segments; 4 domains; 4 binding sites; 15 post-translational modification sites.
Ancestry evidence: 803 variants have ancestry-specific frequency data.
Structural context: 2,704 variants have structural context.
PTM context: 73 variants overlap post-translational modification sites.
3D hotspots: 2 hotspot clusters were identified. Clusters at residues 463-567 (intolerant, 24 variants); residues 606-759 (intolerant, 10 variants).
Allosteric analysis: 10 functional sites were identified.
gnomAD gene constraint: pLI 1.00 (highly intolerant of loss-of-function variation); LOEUF 0.20; missense Z-score 4.59.

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 FGFR2 variants

Examples include M1?, M1V, V2I, V2L, S3C, S3G, S3I, S3N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

FGFR2 analysis run — FGFR2 (3,663 variants) — completed 2026-08-10