Is CEL p.Val670fs (c.2008_2039del) pathogenic?

CEL p.Val670fs (c.20082039del) is classified Uncertain significance in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). Ultra-rare (popmax 0.0359%, nfe); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Val670fs (c.2008_2039del)?

CEL p.Val670fs (c.2008_2039del) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Val670fs (c.2008_2039del) in the general population?

CEL p.Val670fs (c.2008_2039del) is ultra-rare (popmax 0.0359%, nfe) (gnomAD).

How is MODY inherited?

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

CEL p.Val670fs

c.2008_2039del · VCV3779042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0359%, nfe)

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 -2
Overall
CADD	22.5	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 0.0359% European (non-Finnish) · 151/420,714 alleles

Filtering AF 0.0312% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.0343% 191/557,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0932%	1,074
Remaining individualsnot grpmax-eligible	0.054%	1,851
Ashkenazi Jewishnot grpmax-eligible	0.0457%	2,188
European (non-Finnish)grpmax	0.0359%	2,786
Admixed American	0.0296%	3,375
African / African-American	0.0078%	12,821
South Asian	0.00585%	17,083

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val670fs
Coding: c.2008_2039del
MANE Select: NM_001807
Type: Deletion
Location: chr9:133071501 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 670: 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.Asp719fs Uncertain significance ★ same condition
CEL p.Gly166fs Uncertain significance ★ same condition
CEL p.Gly721_Ser731del 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-val670fs (accessed [today's date]).

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