FGFR2 p.Val516=
c.1548G>A · rs200522893 · VCV299001
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.91%, sas)
Conditions
4
Beare-Stevenson cutis gyrata 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 4.9 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 12.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.91%
South Asian · 1,742/91,082 alleles
Filtering AF
1.84%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.81%
Overall
0.116%
1,866/1,614,038 alleles · low-frequency
exomes 1,766/1,461,710 · genomes 100/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.91% | 52 |
| Remaining individualsnot grpmax-eligible | 0.118% | 845 |
| Middle Eastern | 0.099% | 1,010 |
| African / African-American | 0.00799% | 12,510 |
| East Asian | 0.00669% | 14,957 |
| European (non-Finnish) | 0.00297% | 33,714 |
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.Val516=
- Coding
- c.1548G>A
- MANE Select
- NM_000141
- dbSNP
- rs200522893
- Type
- single nucleotide variant
- Location
- chr10:121500839 (GRCh38)
- Gene constraint
- LOEUF 0.278 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.33 · 65 PDB
- Residue 516
- a β-strand; the protein kinase domain
Similar variants
- FGFR2 c.1084+3A>G 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
- FGFR2 p.Asn549His Pathogenic/Likely pathogenic ★★ same condition
- FGFR2 p.Asp336Gly Pathogenic/Likely pathogenic ★★ same condition
- FGFR2 p.Cys278Phe 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-val516 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown