Is CEL p.Glu298Ala (c.893A>C) pathogenic?

CEL p.Glu298Ala (c.893A>C) is classified Uncertain significance in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-19). Very rare (popmax 0.00892%, eas); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Glu298Ala (c.893A>C)?

CEL p.Glu298Ala (c.893A>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEL p.Glu298Ala (c.893A>C) in the general population?

CEL p.Glu298Ala (c.893A>C) is very rare (popmax 0.00892%, eas) (gnomAD).

CEL p.Glu298Ala

c.893A>C · rs377579138 · VCV2619332

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.154	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,610 bp · p 0.015 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,846 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00031% 5/1,613,180 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,212
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Glu298Ala
Coding: c.893A>C
MANE Select: NM_001807
dbSNP: rs377579138
Type: single nucleotide variant
Location: chr9:133067203 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEL p.Glu298Gly Uncertain significance ★ same residue
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

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-glu298ala (accessed [today's date]).

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