Is FGFR2 p.Pro263= (c.789G>A) pathogenic?

FGFR2 p.Pro263= (c.789G>A) is classified Benign/Likely benign in FGFR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-02). Rare (popmax 0.182%, amr); Associated with FGFR2-related craniosynostosis.

What condition is associated with FGFR2 p.Pro263= (c.789G>A)?

FGFR2 p.Pro263= (c.789G>A) is associated with FGFR2-related craniosynostosis (ClinVar).

How common is FGFR2 p.Pro263= (c.789G>A) in the general population?

FGFR2 p.Pro263= (c.789G>A) is rare (popmax 0.182%, amr) (gnomAD).

FGFR2 p.Pro263=

c.789G>A · rs138315382 · VCV706415

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.182%, amr)

Conditions

FGFR2-related craniosynostosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.6	GERP -4.3
Overall
CADD	1.772	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.182% Admixed American · 109/60,006 alleles

Filtering AF 0.154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.144%

Overall 0.00731% 118/1,613,908 alleles · rare exomes 109/1,461,608 · genomes 9/152,300 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.182%	551
Remaining individualsnot grpmax-eligible	0.0048%	20,831
South Asian	0.00439%	22,766
African / African-American	0.00266%	37,526

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FGFR2
Protein: p.Pro263=
Coding: c.789G>A
MANE Select: NM_000141
dbSNP: rs138315382
Type: single nucleotide variant
Location: chr10:121520129 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB
Residue 263: a UniProt-annotated variant site (in cs); the ig-like c2-type 3 domain

Full FGFR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FGFR2-related craniosynostosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGFR2 p.Pro263Leu Uncertain significance ★★ ⚠ same residue
FGFR2 p.Pro263Arg Uncertain significance ★ ⚠ same residue
FGFR2 c.1084+1G>A Pathogenic ★★ same condition
FGFR2 c.1084+2T>C Pathogenic ★★ same condition
FGFR2 c.1084+3A>G Pathogenic ★★ same condition
FGFR2 c.940-1G>T Pathogenic ★★ same condition
FGFR2 p.Ala648Thr Pathogenic ★★ same condition
FGFR2 p.Asp321Ala Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/fgfr2-p-pro263 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown