CEL p.Val446Ile
c.1336G>A · rs375516932 · VCV2221286
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0401%, eas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.032 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -3.7 |
| Regional constraint | o/e 0.75 | unconstrained · MANE · 651 bp · p 0.0028 · regional, not allelic |
| Overall | ||
| CADD | 0.001 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0401%
East Asian · 18/44,876 alleles
Filtering AF
0.0259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0214%
Overall
0.00359%
58/1,613,724 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0401% | 2,493 |
| Middle Eastern | 0.0164% | 6,084 |
| South Asian | 0.00439% | 22,770 |
| European (non-Finnish) | 0.00271% | 36,874 |
| Admixed American | 0.00167% | 59,958 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,468 |
| African / African-American | 0.00134% | 74,784 |
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.Val446Ile
- Coding
- c.1336G>A
- MANE Select
- NM_001807
- dbSNP
- rs375516932
- Type
- single nucleotide variant
- Location
- chr9:133070510 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.10 · 7 PDB
Similar variants
- CEL p.Ala295Ser Uncertain significance ★★ same condition
- CEL p.Ala548Glu Uncertain significance ★★ same condition
- CEL p.Arg185Trp Uncertain significance ★★ same condition
- CEL p.Arg443Trp Uncertain significance ★★ same condition
- CEL p.Gln460Arg Uncertain significance ★★ same condition
- CEL p.Glu710Lys Uncertain significance ★★ same condition
- CEL p.Gly147Ser Uncertain significance ★★ same condition
- CEL p.His68Leu Uncertain significance ★★ same condition
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-val446ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown