Is CEL p.Ala601fs (c.1801del) pathogenic?

CEL p.Ala601fs (c.1801del) is classified Conflicting classifications of pathogenicity in CEL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-31). Rare (popmax 0.494%, sas); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Ala601fs (c.1801del)?

CEL p.Ala601fs (c.1801del) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Ala601fs (c.1801del) in the general population?

CEL p.Ala601fs (c.1801del) is rare (popmax 0.494%, sas) (gnomAD).

How is MODY inherited?

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

CEL p.Ala601fs

c.1801del · VCV3893039

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.494%, 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 -20	GERP -1.4
Overall
CADD	20.7	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 0.494% South Asian · 245/49,582 alleles

Filtering AF 0.443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.424%

Overall 0.128% 711/555,982 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.494%	202
Middle Eastern	0.474%	211
Ashkenazi Jewishnot grpmax-eligible	0.306%	327
Amishnot grpmax-eligible	0.244%	410
Remaining individualsnot grpmax-eligible	0.177%	564
Finnishnot grpmax-eligible	0.115%	871
European (non-Finnish)	0.0934%	1,071
Admixed American	0.0209%	4,777
African / African-American	0.0115%	8,683

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.Ala601fs
Coding: c.1801del
MANE Select: NM_001807
Type: Deletion
Location: chr9:133071300 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 601: 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.Ala601Pro Likely benign ★★ same residue
CEL p.Val626fs Likely pathogenic ★ same condition
CEL p.557ATPVPPTGDSE[1] Uncertain significance ★ same condition
CEL p.Ala601Gly Uncertain significance ★ same residue
CEL p.Ala733_Lys743del Uncertain significance ★ same condition
CEL p.Asp719fs Uncertain significance ★ same condition
CEL p.Gly166fs 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-ala601fs (accessed [today's date]).

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