Is CEL p.Ile352Val (c.1054A>G) pathogenic?

CEL p.Ile352Val (c.1054A>G) is classified Uncertain significance in CEL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-19). Very rare (popmax 8.87e-05%, nfe); Associated with CEL-related disorder.

What condition is associated with CEL p.Ile352Val (c.1054A>G)?

CEL p.Ile352Val (c.1054A>G) is associated with CEL-related disorder (ClinVar).

How common is CEL p.Ile352Val (c.1054A>G) in the general population?

CEL p.Ile352Val (c.1054A>G) is very rare (popmax 8.87e-05%, nfe) (gnomAD).

CEL p.Ile352Val

c.1054A>G · VCV3348281

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.87e-05%, nfe)

Conditions

CEL-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.054	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP 0.6
Regional constraint	o/e 0.22	constrained · MANE · 158 bp · p 2.1e-12 · regional, not allelic
Overall
CADD	5.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.87e-05% European (non-Finnish) · 1/1,127,750 alleles

Overall 6.52e-05% 1/1,534,050 alleles · very rare exomes 1/1,386,280 · genomes 0/147,770 · joint denominator

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.Ile352Val
Coding: c.1054A>G
MANE Select: NM_001807
Type: single nucleotide variant
Location: chr9:133068830 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 352: an α-helix

Full CEL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CEL-related disorder

Similar variants

CEL p.Thr471fs Conflicting classifications of pathogenicity ★ same condition
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-ile352val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown