CEL p.Arg474Trp
c.1420C>T · rs749712301 · VCV1216299
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0317%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.082 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.2 | GERP -0.5, phastCons 1 |
| Regional constraint | o/e 0.75 | unconstrained · MANE · 651 bp · p 0.0028 · regional, not allelic |
| Overall | ||
| CADD | 18.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0317%
Admixed American · 19/60,004 alleles
Filtering AF
0.0207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0172%
Overall
0.00248%
40/1,614,008 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0317% | 3,158 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
| Finnishnot grpmax-eligible | 0.00156% | 64,032 |
| European (non-Finnish) | 0.00144% | 69,413 |
| South Asian | 0.0011% | 91,086 |
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
- CEL
- Protein
- p.Arg474Trp
- Coding
- c.1420C>T
- MANE Select
- NM_001807
- dbSNP
- rs749712301
- Type
- single nucleotide variant
- Location
- chr9:133070594 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.10 · 7 PDB
Similar variants
- CEL p.Arg474Gln Uncertain significance ★ same residue
- CEL c.67-3C>A Uncertain significance ★★ same type
- CEL p.Ala295Ser Uncertain significance ★★ same type
- CEL p.Ala548Glu Uncertain significance ★★ same type
- CEL p.Ala722Val Uncertain significance ★★ same type
- CEL p.Arg116Gln Uncertain significance ★★ same type
- CEL p.Arg185Trp Uncertain significance ★★ same type
- CEL p.Arg443Trp Uncertain significance ★★ 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/cel-p-arg474trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown