Is FGFR2 p.Pro413= (c.1239G>A) pathogenic?

FGFR2 p.Pro413= (c.1239G>A) is classified Conflicting classifications of pathogenicity in FGFR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-03-18). Ultra-rare (popmax 0.0223%, eas); Associated with Saethre-Chotzen syndrome.

What condition is associated with FGFR2 p.Pro413= (c.1239G>A)?

FGFR2 p.Pro413= (c.1239G>A) is associated with Saethre-Chotzen syndrome, Crouzon syndrome, Beare-Stevenson cutis gyrata syndrome (ClinVar).

How common is FGFR2 p.Pro413= (c.1239G>A) in the general population?

FGFR2 p.Pro413= (c.1239G>A) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

FGFR2 p.Pro413=

c.1239G>A · rs147674677 · VCV299003

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 0.0223%, eas)

Conditions

Saethre-Chotzen syndrome

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 -5.2	GERP -4.3
Overall
CADD	5.198	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,876 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00917%

Overall 0.00378% 61/1,614,150 alleles · ultra-rare exomes 56/1,461,890 · genomes 5/152,260 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,488
Middle Eastern	0.0165%	6,062
South Asian	0.00878%	11,386
African / African-American	0.00666%	15,005
European (non-Finnish)	0.00305%	32,778
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.Pro413=
Coding: c.1239G>A
MANE Select: NM_000141
dbSNP: rs147674677
Type: single nucleotide variant
Location: chr10:121515165 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB

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

Disease context

Saethre-Chotzen syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

FGFR2 p.Pro413Leu Uncertain significance ★★ ⚠ same residue
FGFR2 c.1084+3A>G 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
FGFR2 p.Asn549His Pathogenic/Likely pathogenic ★★ same condition
FGFR2 p.Asp336Gly 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-pro413 (accessed [today's date]).

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