FGFR3 p.Asp641=
c.1923C>T · rs148104605 · VCV497445
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.264%, 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 -12 | GERP -3.7 |
| Overall | ||
| CADD | 0.686 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.264%
African / African-American · 198/75,046 alleles
Filtering AF
0.234%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.222%
Overall
0.0188%
304/1,613,140 alleles · rare
exomes 194/1,460,814 · genomes 110/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.264% | 379 |
| Amishnot grpmax-eligible | 0.11% | 912 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,839 |
| Admixed American | 0.02% | 4,991 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.00585% | 17,098 |
| South Asian | 0.0011% | 91,058 |
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.Asp641=
- Coding
- c.1923C>T
- MANE Select
- NM_000142
- dbSNP
- rs148104605
- Type
- single nucleotide variant
- Location
- chr4:1806137 (GRCh38)
- Gene constraint
- LOEUF 0.458 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.25 · 16 PDB
- Residue 641
- an α-helix; the protein kinase domain
Similar variants
- FGFR3 p.Asp641Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
- FGFR3 p.Asp641Gly Uncertain significance ★ ⚠ same residue
- FGFR3 p.Asp641Val Uncertain significance ★ ⚠ same residue
- FGFR3 p.Asp641Ile 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
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-asp641 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown