Is CEL p.Arg185Gln (c.554G>A) pathogenic?

CEL p.Arg185Gln (c.554G>A) is classified Likely benign in CEL (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-06-01). Rare (popmax 0.163%, nfe); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Arg185Gln (c.554G>A)?

CEL p.Arg185Gln (c.554G>A) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Arg185Gln (c.554G>A) in the general population?

CEL p.Arg185Gln (c.554G>A) is rare (popmax 0.163%, nfe) (gnomAD).

How is MODY inherited?

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

CEL p.Arg185Gln

c.554G>A · rs141665160 · VCV1219929

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.163%, nfe)

Conditions

maturity-onset diabetes of the young type 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.213	benign-leaning
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.7	GERP -2.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,610 bp · p 0.015 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% European (non-Finnish) · 1,926/1,180,026 alleles

Filtering AF 0.157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.155%

Overall 0.124% 2,004/1,614,052 alleles · rare exomes 1,892/1,461,740 · genomes 112/152,312 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.163%	613
Remaining individualsnot grpmax-eligible	0.0784%	1,276
African / African-American	0.0293%	3,411
Admixed American	0.00666%	15,006
East Asian	0.00223%	44,878
Finnishnot grpmax-eligible	0.00156%	63,910
South Asian	0.0011%	91,086

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.Arg185Gln
Coding: c.554G>A
MANE Select: NM_001807
dbSNP: rs141665160
Type: single nucleotide variant
Location: chr9:133066545 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 185: 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.Arg185Trp 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.Arg443Trp Uncertain significance ★★ same condition
CEL p.Asn37Ser 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-arg185gln (accessed [today's date]).

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