FGFR3 p.Ala489=
c.1467G>A · VCV3704054
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0033%, sas)
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 -13 | GERP -3.7 |
| Overall | ||
| CADD | 2.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0033%
South Asian · 3/91,024 alleles
Filtering AF
0.000876%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000496%
8/1,612,232 alleles · very rare
exomes 7/1,460,008 · genomes 1/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0033% | 30,341 |
| Admixed American | 0.00167% | 59,988 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,436 |
| European (non-Finnish) | 0.000254% | 393,227 |
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.Ala489=
- Coding
- c.1467G>A
- MANE Select
- NM_000142
- Type
- single nucleotide variant
- Location
- chr4:1805409 (GRCh38)
- Gene constraint
- LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.25 · 16 PDB
- Residue 489
- the protein kinase domain; a β-strand
Similar variants
- FGFR3 p.Ala489Val 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-ala489 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown