Is CEL p.Gln476Arg (c.1427A>G) pathogenic?

CEL p.Gln476Arg (c.1427A>G) is classified Conflicting classifications of pathogenicity in CEL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-02-01). Rare (popmax 0.103%, amr); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Gln476Arg (c.1427A>G)?

CEL p.Gln476Arg (c.1427A>G) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Gln476Arg (c.1427A>G) in the general population?

CEL p.Gln476Arg (c.1427A>G) is rare (popmax 0.103%, amr) (gnomAD).

How is MODY inherited?

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

CEL p.Gln476Arg

c.1427A>G · rs201074543 · VCV2502160

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.103%, amr)

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.
REVEL	0.081	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.83, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 651 bp · p 0.0028 · regional, not allelic
Overall
CADD	17.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% Admixed American · 60/58,374 alleles

Filtering AF 0.0819% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0744%

Overall 0.0162% 259/1,597,776 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.103%	973
Remaining individualsnot grpmax-eligible	0.0339%	2,954
Middle Eastern	0.0166%	6,010
European (non-Finnish)	0.0127%	7,902
Finnishnot grpmax-eligible	0.0112%	8,957
South Asian	0.0111%	9,049
African / African-American	0.0108%	9,279
East Asian	0.00898%	11,142

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.Gln476Arg
Coding: c.1427A>G
MANE Select: NM_001807
dbSNP: rs201074543
Type: single nucleotide variant
Location: chr9:133070601 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 476: an α-helix

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.Gln476Pro Uncertain significance ★ same residue
CEL c.67-3C>A Uncertain significance ★★ same condition
CEL p.Ala295Ser Uncertain significance ★★ same condition
CEL p.Ala548Glu Uncertain significance ★★ same condition
CEL p.Ala722Val Uncertain significance ★★ same condition
CEL p.Arg116Gln Uncertain significance ★★ same condition
CEL p.Arg185Trp Uncertain significance ★★ same condition
CEL p.Arg443Trp 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-gln476arg (accessed [today's date]).

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