Is FGFR2 p.Phe600= (c.1800C>T) pathogenic?

FGFR2 p.Phe600= (c.1800C>T) is classified Uncertain significance in FGFR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). Very rare (popmax 0.00136%, nfe); Associated with bent bone dysplasia syndrome 1.

What condition is associated with FGFR2 p.Phe600= (c.1800C>T)?

FGFR2 p.Phe600= (c.1800C>T) is associated with bent bone dysplasia syndrome 1, gastric cancer, Apert syndrome (ClinVar).

How common is FGFR2 p.Phe600= (c.1800C>T) in the general population?

FGFR2 p.Phe600= (c.1800C>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

How is FGFR2-related bent bone dysplasia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

FGFR2 p.Phe600=

c.1800C>T · VCV3590823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Conditions

bent bone dysplasia syndrome 1

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 3.4	GERP -1.3, phastCons 1
Overall
CADD	9.268	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,180,014 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00105% 17/1,613,646 alleles · very rare exomes 15/1,461,770 · genomes 2/151,876 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00136%	73,751
African / African-American	0.00134%	74,814

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.Phe600=
Coding: c.1800C>T
MANE Select: NM_000141
Type: single nucleotide variant
Location: chr10:121496595 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB
Residue 600: an α-helix; the protein kinase domain

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

Disease context

bent bone dysplasia syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastric cancer Apert syndrome Saethre-Chotzen syndrome Pfeiffer syndrome Jackson-Weiss syndrome Crouzon syndrome Beare-Stevenson cutis gyrata syndrome familial scaphocephaly syndrome, McGillivray type Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis LADD syndrome 1

For FGFR2-related bent bone dysplasia (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Neonatal

Similar variants

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.940-2A>C Pathogenic ★★ same condition
FGFR2 p.Ala314Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
FGFR2 p.Ala337Pro Pathogenic/Likely pathogenic ★★ same condition
FGFR2 p.Ala344= Pathogenic ★★ same condition
FGFR2 p.Ala344Gly 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-phe600 (accessed [today's date]).

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