Is FGFR2 p.Val232= (c.696A>G) pathogenic?

FGFR2 p.Val232= (c.696A>G) is classified Benign in FGFR2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-05-08). Common (popmax 90.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with FGFR2-related craniosynostosis.

What condition is associated with FGFR2 p.Val232= (c.696A>G)?

FGFR2 p.Val232= (c.696A>G) is associated with FGFR2-related craniosynostosis, Saethre-Chotzen syndrome, Crouzon syndrome (ClinVar).

FGFR2 p.Val232=

Q: How common is FGFR2 p.Val232= (c.696A>G) in the general population?

FGFR2 p.Val232= (c.696A>G) is common (popmax 90.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.696A>G · rs1047100 · VCV255319

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 90.4%, eas) — too common for a highly-penetrant pathogenic allele

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 0.57	GERP -1.1, phastCons 1
Overall
CADD	10.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 90.4% East Asian · 40,551/44,842 alleles

Filtering AF 89.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 89.4%

Overall 77.7% 1,253,875/1,613,866 alleles · common exomes 1,136,925/1,461,792 · genomes 116,950/152,074 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	90.4%	1
Middle Eastern	82.4%	1
Ashkenazi Jewishnot grpmax-eligible	82%	1
Admixed American	79.5%	1
Remaining individualsnot grpmax-eligible	79.3%	1
Amishnot grpmax-eligible	77.9%	1
European (non-Finnish)	77.4%	1
African / African-American	75.4%	1
Finnishnot grpmax-eligible	75.3%	1
South Asian	74.6%	1

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.Val232=
Coding: c.696A>G
MANE Select: NM_000141
dbSNP: rs1047100
Type: single nucleotide variant
Location: chr10:121538644 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB
Residue 232: a β-strand; the ig-like c2-type 2 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-val232 (accessed [today's date]).

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