Is CEL p.Val714fs (c.2139dup) pathogenic?

CEL p.Val714fs (c.2139dup) is classified Likely pathogenic in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). Very rare (popmax 0.00264%, eas); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Val714fs (c.2139dup)?

CEL p.Val714fs (c.2139dup) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Val714fs (c.2139dup) in the general population?

CEL p.Val714fs (c.2139dup) is very rare (popmax 0.00264%, eas) (gnomAD).

How is MODY inherited?

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

CEL p.Val714fs

c.2139dup · VCV3596587

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00264%, eas)

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 -7.4	GERP -0.71
Overall
CADD	18.84	PHRED · no single calibrated threshold — expert panels disagree
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 0.00264% East Asian · 1/37,814 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000843%

Overall 0.00149% 20/1,341,852 alleles · very rare exomes 19/1,283,622 · genomes 1/58,230 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00264%	37,814
South Asian	0.00244%	40,965
European (non-Finnish)	0.00169%	59,034

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.Val714fs
Coding: c.2139dup
MANE Select: NM_001807
Type: Duplication
Location: chr9:133071636 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 714: 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 c.895+2dup Uncertain significance ★★ same condition
CEL p.Asp204fs Uncertain significance ★ same condition
CEL p.Gly688_Ala689insProProProValProProThrGlyAspSerGly Uncertain significance ★ same condition
CEL p.Thr695fs Uncertain significance ★ same condition
CEL p.Val604fs Uncertain significance ★ same condition
CEL p.Val637fs Uncertain significance ★ same condition
CEL p.Val681fs Uncertain significance ★ same condition
CEL p.Val692fs Conflicting classifications of pathogenicity ★ 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-val714fs (accessed [today's date]).

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