FGFR3 p.Pro694=
c.2082G>A · rs765659195 · VCV707579
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0132%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.249 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -3.7 |
| Overall | ||
| CADD | 0.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0132%
South Asian · 12/91,086 alleles
Filtering AF
0.00751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00593%
Overall
0.00415%
67/1,613,018 alleles · ultra-rare
exomes 51/1,460,928 · genomes 16/152,090 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0132% | 7,590 |
| African / African-American | 0.0107% | 9,361 |
| Admixed American | 0.00667% | 14,997 |
| East Asian | 0.00446% | 22,440 |
| European (non-Finnish) | 0.00331% | 30,255 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,472 |
| Finnishnot grpmax-eligible | 0.00158% | 63,150 |
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
- FGFR3
- Protein
- p.Pro694=
- Coding
- c.2082G>A
- MANE Select
- NM_000142
- dbSNP
- rs765659195
- Type
- single nucleotide variant
- Location
- chr4:1806597 (GRCh38)
- Gene constraint
- LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.25 · 16 PDB
- Residue 694
- the protein kinase domain
Similar variants
- FGFR3 p.Pro694Leu Uncertain significance ★★ ⚠ same residue
- FGFR3 p.Ala391Glu Pathogenic ★★ same type
- FGFR3 p.Arg248Cys Pathogenic ★★ same type
- FGFR3 p.Arg621His Pathogenic/Likely pathogenic ★★ same type
- FGFR3 p.Asn540Asp Pathogenic/Likely pathogenic ★★ same type
- FGFR3 p.Asn540Lys Pathogenic ★★ same type
- FGFR3 p.Asn540Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
- FGFR3 p.Asn540Thr Pathogenic/Likely pathogenic ★★ same type
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/fgfr3-p-pro694 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown