Is CEL p.Asp719fs (c.2154_2163del) pathogenic?

CEL p.Asp719fs (c.21542163del) is classified Uncertain significance in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). Very rare (popmax 0.00339%, sas); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Asp719fs (c.2154_2163del)?

CEL p.Asp719fs (c.2154_2163del) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Asp719fs (c.2154_2163del) in the general population?

CEL p.Asp719fs (c.2154_2163del) is very rare (popmax 0.00339%, sas) (gnomAD).

How is MODY inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

CEL p.Asp719fs

c.2154_2163del · VCV3893284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00339%, sas)

Conditions

maturity-onset diabetes of the young type 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -10	GERP -0.79
Region caveats
Repeat context	tandem	chr9:133080625 segmental duplication, simple repeat · ambiguous alignment · reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00339% South Asian · 3/88,486 alleles

Filtering AF 0.000901% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00045%

Overall 0.000211% 3/1,419,958 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.Asp719fs
Coding: c.2154_2163del
MANE Select: NM_001807
Type: Deletion
Location: chr9:133071652 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 719: the 'disordered' region; the '17 x 11 aa tandem repeats, glycodomain, o-linked (mucin type)' region

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

Disease context

maturity-onset diabetes of the young type 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MODY (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CEL p.Val593fs Likely pathogenic ★★ same condition
CEL p.Val626fs Likely pathogenic ★ same condition
CEL p.557ATPVPPTGDSE[1] Uncertain significance ★ same condition
CEL p.Ala601fs Conflicting classifications of pathogenicity ★ same condition
CEL p.Ala733_Lys743del Uncertain significance ★ same condition
CEL p.Gly166fs Uncertain significance ★ same condition
CEL p.Gly721_Ser731del Uncertain significance ★ same condition
CEL p.Gly721_Ser742del 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-asp719fs (accessed [today's date]).

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