Is FGFR2 p.Ser252= (c.756G>A) pathogenic?

FGFR2 p.Ser252= (c.756G>A) is classified Likely benign in FGFR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-24). Ultra-rare (popmax 0.024%, afr); Associated with FGFR2-related craniosynostosis.

What condition is associated with FGFR2 p.Ser252= (c.756G>A)?

FGFR2 p.Ser252= (c.756G>A) is associated with FGFR2-related craniosynostosis (ClinVar).

How common is FGFR2 p.Ser252= (c.756G>A) in the general population?

FGFR2 p.Ser252= (c.756G>A) is ultra-rare (popmax 0.024%, afr) (gnomAD).

FGFR2 p.Ser252=

c.756G>A · rs138769323 · VCV1113095

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Conditions

FGFR2-related craniosynostosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -11	GERP -4.3
Overall
CADD	1.969	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/75,002 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00198% 32/1,613,066 alleles · ultra-rare exomes 27/1,460,828 · genomes 5/152,238 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,167
Admixed American	0.00333%	29,985
Remaining individualsnot grpmax-eligible	0.0016%	62,456
South Asian	0.0011%	90,984
European (non-Finnish)	0.000848%	117,951

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.Ser252=
Coding: c.756G>A
MANE Select: NM_000141
dbSNP: rs138769323
Type: single nucleotide variant
Location: chr10:121520162 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB
Residue 252: a UniProt-annotated variant site (in ps); a UniProt-annotated variant site (in aprs; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in); a UniProt-annotated variant site (in aprs and ps; common mutation)

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

Disease context

FGFR2-related craniosynostosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGFR2 p.Ser252Tyr Uncertain significance ★ same residue
FGFR2 p.Ser252Trp Pathogenic ★★ same residue
FGFR2 p.Ser252Leu Conflicting classifications of pathogenicity ★ ⚠ 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>T Pathogenic ★★ same condition
FGFR2 p.Ala648Thr 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-ser252 (accessed [today's date]).

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