FGFR3 p.Ser221=
c.663G>A · rs114421370 · VCV465355
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 10 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.61%, afr)
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 -20 | GERP -3.7 |
| Overall | ||
| CADD | 2.205 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.61%
African / African-American · 1,204/75,010 alleles
Filtering AF
1.53%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.5%
Overall
0.0913%
1,472/1,611,412 alleles · low-frequency
exomes 775/1,459,064 · genomes 697/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.61% | 62 |
| Remaining individualsnot grpmax-eligible | 0.146% | 686 |
| Admixed American | 0.125% | 799 |
| Ashkenazi Jewishnot grpmax-eligible | 0.122% | 820 |
| Middle Eastern | 0.0991% | 1,009 |
| South Asian | 0.0077% | 12,981 |
| European (non-Finnish) | 0.00449% | 22,252 |
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.Ser221=
- Coding
- c.663G>A
- MANE Select
- NM_000142
- dbSNP
- rs114421370
- Type
- single nucleotide variant
- Location
- chr4:1801667 (GRCh38)
- Gene constraint
- LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.25 · 16 PDB
- Residue 221
- the ig-like c2-type 2 domain; an α-helix
Similar variants
- FGFR3 p.Ser221Leu 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-ser221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown