Is FGFR2 p.Ala67= (c.201C>T) pathogenic?

FGFR2 p.Ala67= (c.201C>T) is classified Conflicting classifications of pathogenicity in FGFR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-18). Ultra-rare (popmax 0.013%, nfe); Associated with FGFR2-related craniosynostosis.

What condition is associated with FGFR2 p.Ala67= (c.201C>T)?

FGFR2 p.Ala67= (c.201C>T) is associated with FGFR2-related craniosynostosis, Saethre-Chotzen syndrome, Crouzon syndrome (ClinVar).

How common is FGFR2 p.Ala67= (c.201C>T) in the general population?

FGFR2 p.Ala67= (c.201C>T) is ultra-rare (popmax 0.013%, nfe) (gnomAD).

FGFR2 p.Ala67=

c.201C>T · rs200386134 · VCV877763

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.013%, 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 2.6	GERP -0.14, phastCons 1
Overall
CADD	13.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.013% European (non-Finnish) · 153/1,180,042 alleles

Filtering AF 0.0113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00997% 161/1,614,046 alleles · ultra-rare exomes 154/1,461,892 · genomes 7/152,154 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.013%	7,713
African / African-American	0.00534%	18,728
East Asian	0.00446%	22,445
Remaining individualsnot grpmax-eligible	0.0016%	62,488
South Asian	0.0011%	91,088

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.Ala67=
Coding: c.201C>T
MANE Select: NM_000141
dbSNP: rs200386134
Type: single nucleotide variant
Location: chr10:121565613 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB
Residue 67: the ig-like c2-type 1 domain

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

Disease context

Also linked: Saethre-Chotzen syndrome Crouzon syndrome Beare-Stevenson cutis gyrata syndrome craniosynostosis

Similar variants

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.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-ala67 (accessed [today's date]).

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