FGFR3 p.Pro735=
c.2205C>G · rs145020302 · VCV255338
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.05%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.111 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -2.3, phastCons 0.001 |
| Overall | ||
| CADD | 2.922 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.05%
African / African-American · 790/75,006 alleles
Filtering AF
0.992%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.968%
Overall
0.0547%
881/1,611,616 alleles · low-frequency
exomes 433/1,459,338 · genomes 448/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.05% | 95 |
| Admixed American | 0.0885% | 1,130 |
| Remaining individualsnot grpmax-eligible | 0.0513% | 1,951 |
| Middle Eastern | 0.0165% | 6,060 |
| South Asian | 0.0022% | 45,428 |
| European (non-Finnish) | 0.000254% | 393,195 |
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.Pro735=
- Coding
- c.2205C>G
- MANE Select
- NM_000142
- dbSNP
- rs145020302
- Type
- single nucleotide variant
- Location
- chr4:1806865 (GRCh38)
- Gene constraint
- LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.25 · 16 PDB
- Residue 735
- an α-helix; the protein kinase domain
Similar variants
- FGFR3 p.Pro735Leu 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-pro735 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown