CEL p.Arg540Cys
c.1618C>T · VCV4905241
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.199 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.23 | GERP 0.16 |
| Regional constraint | o/e 1.11 | unconstrained · MANE · 642 bp · p 0.096 · regional, not allelic |
| Overall | ||
| CADD | 20.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,838 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0078%
Overall
0.00447%
72/1,609,632 alleles · ultra-rare
exomes 66/1,457,572 · genomes 6/152,060 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,982 |
| Middle Eastern | 0.0165% | 6,060 |
| South Asian | 0.0143% | 7,005 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,616 |
| European (non-Finnish) | 0.00365% | 27,434 |
| Admixed American | 0.00167% | 59,956 |
| Finnishnot grpmax-eligible | 0.00166% | 60,132 |
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.Arg540Cys
- Coding
- c.1618C>T
- MANE Select
- NM_001807
- Type
- single nucleotide variant
- Location
- chr9:133071120 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.10 · 7 PDB
- Residue 540
- an α-helix
Similar variants
- CEL p.Arg540His Benign/Likely benign ★★ 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-arg540cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown