CEL p.Arg443Gln
c.1328G>A · VCV3776559
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.2 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.98 | acceptor gain · deltas |
| Pangolin | Δ0.83 | gain · loss 0.50 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP -1.8, phastCons 1 |
| Regional constraint | o/e 0.75 | unconstrained · MANE · 651 bp · p 0.0028 · regional, not allelic |
| Overall | ||
| CADD | 35.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,058 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00124%
20/1,613,824 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,058 |
| East Asian | 0.0111% | 8,970 |
| Admixed American | 0.00333% | 29,990 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,496 |
| European (non-Finnish) | 0.000932% | 107,271 |
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.Arg443Gln
- Coding
- c.1328G>A
- MANE Select
- NM_001807
- Type
- single nucleotide variant
- Location
- chr9:133070502 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.10 · 7 PDB
Similar variants
- CEL p.Arg443Trp 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.Asn37Ser 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-arg443gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown