FGFR3 p.Pro39=
c.117G>A · rs376223299 · VCV1679985
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0253%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -2 |
| Overall | ||
| CADD | 0.549 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0253%
African / African-American · 19/75,072 alleles
Filtering AF
0.0165%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00447%
72/1,612,532 alleles · ultra-rare
exomes 52/1,460,168 · genomes 20/152,364 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0253% | 3,951 |
| European (non-Finnish) | 0.00398% | 25,105 |
| South Asian | 0.00329% | 30,357 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,236 |
| East Asian | 0.00223% | 44,884 |
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.Pro39=
- Coding
- c.117G>A
- MANE Select
- NM_000142
- dbSNP
- rs376223299
- Type
- single nucleotide variant
- Location
- chr4:1799261 (GRCh38)
- Gene constraint
- LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.25 · 16 PDB
- Residue 39
- the ig-like c2-type 1 domain
Similar variants
- FGFR3 p.Pro39Leu 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-pro39 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown