Is FGFR2 p.Ser252Phe (c.755_756delinsTT) pathogenic?

FGFR2 p.Ser252Phe (c.755756delinsTT) is classified Likely pathogenic in FGFR2 (ClinVar, Single submitter, 3 submitters; last evaluated 2016-09-17). No gnomAD frequency available for this variant; Associated with Apert syndrome.

What condition is associated with FGFR2 p.Ser252Phe (c.755_756delinsTT)?

FGFR2 p.Ser252Phe (c.755_756delinsTT) is associated with Apert syndrome (ClinVar).

How common is FGFR2 p.Ser252Phe (c.755_756delinsTT) in the general population?

FGFR2 p.Ser252Phe (c.755_756delinsTT) is no gnomAD frequency available for this variant (gnomAD).

FGFR2 p.Ser252Phe

c.755_756delinsTT · rs121918498 · VCV13279

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Apert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -4.3
Regional constraint	o/e 0.50	unconstrained · MANE · 34 kb · p 7.3e-17 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FGFR2
Protein: p.Ser252Phe
Coding: c.755_756delinsTT
MANE Select: NM_000141
dbSNP: rs121918498
Type: Indel
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

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

Similar variants

FGFR2 p.Ser252Trp Pathogenic ★★ same residue
FGFR2 p.Ser252Tyr Uncertain significance ★ same residue
FGFR2 p.Ser252_Pro253delinsPheSer Pathogenic same residue
FGFR2 c.1562-9_1562-7delinsAA Uncertain significance ★★ same condition
FGFR2 p.Ser252Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
FGFR2 p.Ser252= Likely benign ★ same residue
FGFR2 p.Pro253Phe Pathogenic same condition
FGFR2 c.1084+3A>G 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-ser252phe (accessed [today's date]).

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