Is FGFR2 p.Ser780= (c.2340A>G) pathogenic?

FGFR2 p.Ser780= (c.2340A>G) is classified Likely benign in FGFR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-20). Very rare (popmax 0.0022%, sas); Associated with FGFR2-related craniosynostosis.

What condition is associated with FGFR2 p.Ser780= (c.2340A>G)?

FGFR2 p.Ser780= (c.2340A>G) is associated with FGFR2-related craniosynostosis (ClinVar).

How common is FGFR2 p.Ser780= (c.2340A>G) in the general population?

FGFR2 p.Ser780= (c.2340A>G) is very rare (popmax 0.0022%, sas) (gnomAD).

FGFR2 p.Ser780=

c.2340A>G · rs2133684293 · VCV2115186

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

FGFR2-related craniosynostosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.265	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.038	GERP -5, phastCons 0.88
Overall
CADD	5.413	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,074 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,614,180 alleles · very rare exomes 2/1,461,892 · genomes 0/152,288 · 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.Ser780=
Coding: c.2340A>G
MANE Select: NM_000141
dbSNP: rs2133684293
Type: single nucleotide variant
Location: chr10:121479983 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB
Residue 780: a modified residue (phosphoserine)

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 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
FGFR2 p.Asp321Ala Pathogenic ★★ same condition
FGFR2 p.Cys342Phe Pathogenic ★★ same condition
FGFR2 p.Cys342Ser 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-ser780 (accessed [today's date]).

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