FGFR3 p.Pro696=
c.2088C>T · rs142884145 · VCV515197
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.168%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.225 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.41 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.7 |
| Overall | ||
| CADD | 1.336 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.168%
African / African-American · 126/75,042 alleles
Filtering AF
0.144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.135%
Overall
0.00955%
154/1,613,212 alleles · rare
exomes 80/1,460,962 · genomes 74/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.168% | 596 |
| Middle Eastern | 0.0165% | 6,054 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,928 |
| South Asian | 0.00659% | 15,181 |
| European (non-Finnish) | 0.00119% | 84,283 |
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.Pro696=
- Coding
- c.2088C>T
- MANE Select
- NM_000142
- dbSNP
- rs142884145
- Type
- single nucleotide variant
- Location
- chr4:1806603 (GRCh38)
- Gene constraint
- LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.25 · 16 PDB
- Residue 696
- the protein kinase domain
Similar variants
- FGFR3 p.Pro696Leu Uncertain significance ★ ⚠ same residue
- FGFR3 p.Pro696Ser 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
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-pro696 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown