Is CEL p.Ala128Val (c.383C>T) pathogenic?

CEL p.Ala128Val (c.383C>T) is classified Conflicting classifications of pathogenicity in CEL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-29). Very rare (popmax 6.84e-05%); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Ala128Val (c.383C>T)?

CEL p.Ala128Val (c.383C>T) is associated with Inborn genetic diseases, type 2 diabetes mellitus (ClinVar).

How common is CEL p.Ala128Val (c.383C>T) in the general population?

CEL p.Ala128Val (c.383C>T) is very rare (popmax 6.84e-05%) (gnomAD).

CEL p.Ala128Val

c.383C>T · rs960508990 · VCV1344530

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.446	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.62	GERP -0.72, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,610 bp · p 0.015 · regional, not allelic
Overall
CADD	19.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,552 alleles · very rare

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.Ala128Val
Coding: c.383C>T
MANE Select: NM_001807
dbSNP: rs960508990
Type: single nucleotide variant
Location: chr9:133065082 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 128: a turn

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

Also linked: type 2 diabetes mellitus

Similar variants

CEL p.Ala128Thr Conflicting classifications of pathogenicity ★ 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-ala128val (accessed [today's date]).

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