Is FGFR2 p.Ser267Pro (c.799T>C) pathogenic?

FGFR2 p.Ser267Pro (c.799T>C) is classified Pathogenic in FGFR2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-07-06). AlphaMissense: likely pathogenic (0.9621); Absent from gnomAD v4.1; Associated with FGFR2-related craniosynostosis.

What condition is associated with FGFR2 p.Ser267Pro (c.799T>C)?

FGFR2 p.Ser267Pro (c.799T>C) is associated with FGFR2-related craniosynostosis, gastric cancer, Pfeiffer syndrome (ClinVar).

How common is FGFR2 p.Ser267Pro (c.799T>C) in the general population?

FGFR2 p.Ser267Pro (c.799T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FGFR2 p.Ser267Pro (c.799T>C)?

AlphaMissense predicts likely pathogenic (score 0.9621) — an in-silico prediction, not a clinical call.

FGFR2 p.Ser267Pro

c.799T>C · rs121918505 · VCV13290

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9621 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FGFR2-related craniosynostosis

Computational evidence

Protein change
AlphaMissense	0.9621	likely pathogenic ✓ concordant with ClinVar
REVEL	0.704	pathogenic-leaning
SaProt	LLR -13.25	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.2, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 34 kb · p 7.3e-17 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FGFR2
Protein: p.Ser267Pro
Coding: c.799T>C
MANE Select: NM_000141
dbSNP: rs121918505
Type: single nucleotide variant
Location: chr10:121520119 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB
Residue 267: a β-strand; 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

Also linked: gastric cancer Pfeiffer syndrome Crouzon syndrome

Similar variants

FGFR2 p.Ser267Thr 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>A Pathogenic/Likely pathogenic ★★ same condition
FGFR2 c.940-1G>T Pathogenic ★★ same condition
FGFR2 p.Ala314Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
FGFR2 p.Ala337Pro Pathogenic/Likely 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-ser267pro (accessed [today's date]).

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