FGFR3 p.Pro63=
c.189G>A · rs140377760 · VCV1187885
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0399%, nfe)
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 -1.5 | GERP -2 |
| Overall | ||
| CADD | 0.486 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0399%
European (non-Finnish) · 471/1,179,890 alleles
Filtering AF
0.0369%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0357%
Overall
0.0317%
511/1,612,588 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0399% | 2,505 |
| Middle Eastern | 0.0331% | 3,021 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,165 |
| Admixed American | 0.0133% | 7,502 |
| African / African-American | 0.0133% | 7,506 |
| East Asian | 0.00891% | 11,219 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,580 |
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.Pro63=
- Coding
- c.189G>A
- MANE Select
- NM_000142
- dbSNP
- rs140377760
- Type
- single nucleotide variant
- Location
- chr4:1799333 (GRCh38)
- Gene constraint
- LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.25 · 16 PDB
- Residue 63
- a disulfide bond; the ig-like c2-type 1 domain
Similar variants
- FGFR3 p.Pro63Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- FGFR3 p.Pro63Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown