Is CEL p.Val120Ile (c.358G>A) pathogenic?

CEL p.Val120Ile (c.358G>A) is classified Conflicting classifications of pathogenicity in CEL (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2022-02-23). Rare (popmax 0.3%, mid); Associated with monogenic diabetes.

What condition is associated with CEL p.Val120Ile (c.358G>A)?

CEL p.Val120Ile (c.358G>A) is associated with monogenic diabetes, maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Val120Ile (c.358G>A) in the general population?

CEL p.Val120Ile (c.358G>A) is rare (popmax 0.3%, mid) (gnomAD).

CEL p.Val120Ile

c.358G>A · rs201336247 · VCV549532

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.3%, mid)

Conditions

monogenic diabetes

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.354	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP -2.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,610 bp · p 0.015 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.3% Middle Eastern · 18/5,996 alleles

Filtering AF 0.194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.16%

Overall 0.0206% 333/1,613,464 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.3%	333
Admixed American	0.09%	1,112
Remaining individualsnot grpmax-eligible	0.024%	4,167
European (non-Finnish)	0.0189%	5,291
African / African-American	0.0187%	5,359
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,402
East Asian	0.00669%	14,958
Finnishnot grpmax-eligible	0.00158%	63,436
South Asian	0.0011%	91,086

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.Val120Ile
Coding: c.358G>A
MANE Select: NM_001807
dbSNP: rs201336247
Type: single nucleotide variant
Location: chr9:133065057 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 120: the 'heparin-binding' region; a β-strand

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

Disease context

monogenic diabetes — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: maturity-onset diabetes of the young type 8

Similar variants

CEL c.67-3C>A Uncertain significance ★★ same condition
CEL p.Ala295Ser Uncertain significance ★★ same condition
CEL p.Ala548Glu Uncertain significance ★★ same condition
CEL p.Ala722Val Uncertain significance ★★ same condition
CEL p.Arg116Gln Uncertain significance ★★ same condition
CEL p.Arg185Trp Uncertain significance ★★ same condition
CEL p.Arg443Trp Uncertain significance ★★ same condition
CEL p.Asn37Ser 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-val120ile (accessed [today's date]).

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