Is FGFR2 p.Phe334= (c.1002T>C) pathogenic?

FGFR2 p.Phe334= (c.1002T>C) is classified Likely benign in FGFR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-13). Very rare (popmax 0.00322%, nfe); Associated with FGFR2-related craniosynostosis.

What condition is associated with FGFR2 p.Phe334= (c.1002T>C)?

FGFR2 p.Phe334= (c.1002T>C) is associated with FGFR2-related craniosynostosis (ClinVar).

How common is FGFR2 p.Phe334= (c.1002T>C) in the general population?

FGFR2 p.Phe334= (c.1002T>C) is very rare (popmax 0.00322%, nfe) (gnomAD).

FGFR2 p.Phe334=

c.1002T>C · rs776683489 · VCV2894826

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

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 8.1	GERP 2.2, phastCons 1
Overall
CADD	13.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 38/1,180,048 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00248% 40/1,614,130 alleles · very rare exomes 36/1,461,886 · genomes 4/152,244 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00322%	31,054
African / African-American	0.00133%	74,940
South Asian	0.0011%	91,092

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.Phe334=
Coding: c.1002T>C
MANE Select: NM_000141
dbSNP: rs776683489
Type: single nucleotide variant
Location: chr10:121517401 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB
Residue 334: an α-helix; 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.Phe334Tyr 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
FGFR2 p.Cys342Phe 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-phe334 (accessed [today's date]).

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