FGFR2 p.Ser431=
c.1293G>A · VCV3716944
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Conditions
1
FGFR2-related craniosynostosis
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 -0.39 | GERP -4.3, phastCons 0.001 |
| Overall | ||
| CADD | 5.529 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/59,998 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.00112%
18/1,613,984 alleles · very rare
exomes 16/1,461,804 · genomes 2/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 19,999 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,252 |
| East Asian | 0.00223% | 44,858 |
| European (non-Finnish) | 0.00102% | 98,331 |
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.Ser431=
- Coding
- c.1293G>A
- MANE Select
- NM_000141
- Type
- single nucleotide variant
- Location
- chr10:121503936 (GRCh38)
- Gene constraint
- LOEUF 0.278 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.33 · 65 PDB
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-ser431 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown