Is FGFR2 p.Arg330= (c.990G>T) pathogenic?

FGFR2 p.Arg330= (c.990G>T) is classified Likely benign in FGFR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-13). Very rare (popmax 0.0022%, sas); Associated with FGFR2-related craniosynostosis.

What condition is associated with FGFR2 p.Arg330= (c.990G>T)?

FGFR2 p.Arg330= (c.990G>T) is associated with FGFR2-related craniosynostosis (ClinVar).

How common is FGFR2 p.Arg330= (c.990G>T) in the general population?

FGFR2 p.Arg330= (c.990G>T) is very rare (popmax 0.0022%, sas) (gnomAD).

FGFR2 p.Arg330=

c.990G>T · rs1388126614 · VCV2050648

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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	donor loss, 43 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Overall
CADD	14.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,084 alleles

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

Overall 0.000186% 3/1,614,228 alleles · very rare exomes 3/1,461,882 · genomes 0/152,346 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,542
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Arg330=
Coding: c.990G>T
MANE Select: NM_000141
dbSNP: rs1388126614
Type: single nucleotide variant
Location: chr10:121517413 (GRCh38)
Gene constraint: LOEUF 0.278 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.33 · 65 PDB
Residue 330: the ig-like c2-type 3 domain

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.Arg330Trp Uncertain significance ★★ ⚠ same residue
FGFR2 p.Arg330Gln 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
FGFR2 p.Asp321Ala 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-arg330 (accessed [today's date]).

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