Is FGFR2 p.Ser587= (c.1761C>T) pathogenic?

FGFR2 p.Ser587= (c.1761C>T) is classified Benign/Likely benign in FGFR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-14). Ultra-rare (popmax 0.0643%, afr); Associated with Apert syndrome.

What condition is associated with FGFR2 p.Ser587= (c.1761C>T)?

FGFR2 p.Ser587= (c.1761C>T) is associated with Apert syndrome, gastric cancer, Saethre-Chotzen syndrome (ClinVar).

How common is FGFR2 p.Ser587= (c.1761C>T) in the general population?

FGFR2 p.Ser587= (c.1761C>T) is ultra-rare (popmax 0.0643%, afr) (gnomAD).

FGFR2 p.Ser587=

c.1761C>T · rs147173572 · VCV724975

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0643%, afr)

Conditions

Apert 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 0.21	GERP -4, phastCons 0.92
Overall
CADD	8.095	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0643% African / African-American · 48/74,664 alleles

Filtering AF 0.0497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0446%

Overall 0.00298% 48/1,612,666 alleles · ultra-rare exomes 12/1,461,288 · genomes 36/151,378 · joint denominator

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.Ser587=
Coding: c.1761C>T
MANE Select: NM_000141
dbSNP: rs147173572
Type: single nucleotide variant
Location: chr10:121496634 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB
Residue 587: a turn; the protein kinase domain

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

Also linked: gastric cancer Saethre-Chotzen syndrome Pfeiffer syndrome Jackson-Weiss syndrome Crouzon syndrome Beare-Stevenson cutis gyrata syndrome LADD syndrome familial scaphocephaly syndrome, McGillivray type bent bone dysplasia syndrome 1 Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis

Similar variants

FGFR2 c.1084+2T>C Pathogenic ★★ same condition
FGFR2 c.1084+3A>G Pathogenic ★★ same condition
FGFR2 c.940-1G>A Pathogenic/Likely pathogenic ★★ same condition
FGFR2 c.940-2A>C 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-ser587 (accessed [today's date]).

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