Is CEL p.Ile316Met (c.948C>G) pathogenic?

CEL p.Ile316Met (c.948C>G) is classified Uncertain significance in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). Ultra-rare (popmax 0.0166%, mid); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Ile316Met (c.948C>G)?

CEL p.Ile316Met (c.948C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEL p.Ile316Met (c.948C>G) in the general population?

CEL p.Ile316Met (c.948C>G) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

CEL p.Ile316Met

c.948C>G · VCV3489964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.434	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -0.93, phastCons 0.12
Regional constraint	o/e 0.22	constrained · MANE · 158 bp · p 2.1e-12 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,034 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000311% 5/1,607,866 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,034
Remaining individualsnot grpmax-eligible	0.00161%	62,280
European (non-Finnish)	0.000255%	392,596

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.Ile316Met
Coding: c.948C>G
MANE Select: NM_001807
Type: single nucleotide variant
Location: chr9:133068724 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 316: a β-strand

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.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-ile316met (accessed [today's date]).

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