Is CEL p.Arg116Gln (c.347G>A) pathogenic?

CEL p.Arg116Gln (c.347G>A) is classified Uncertain significance in CEL (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-06). Rare (popmax 0.104%, afr); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Arg116Gln (c.347G>A)?

CEL p.Arg116Gln (c.347G>A) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Arg116Gln (c.347G>A) in the general population?

CEL p.Arg116Gln (c.347G>A) is rare (popmax 0.104%, afr) (gnomAD).

How is MODY inherited?

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

CEL p.Arg116Gln

c.347G>A · rs199675811 · VCV434691

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.104%, afr)

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	0.055	moderately benign-leaning
Splicing
SpliceAI	Δ0.56	acceptor gain · deltas
Pangolin	Δ0.20	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -2	GERP -2.6
Regional constraint	o/e 0.87	unconstrained · MANE · 6,610 bp · p 0.015 · regional, not allelic
Overall
CADD	8.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.104% African / African-American · 78/74,892 alleles

Filtering AF 0.0855% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.00757% 122/1,611,588 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.104%	960
Remaining individualsnot grpmax-eligible	0.0112%	8,910
Admixed American	0.00833%	12,003
European (non-Finnish)	0.00254%	39,332
Finnishnot grpmax-eligible	0.00158%	63,150
South Asian	0.0011%	90,994

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.Arg116Gln
Coding: c.347G>A
MANE Select: NM_001807
dbSNP: rs199675811
Type: single nucleotide variant
Location: chr9:133065046 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 116: the 'heparin-binding' 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.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.Arg185Trp Uncertain significance ★★ same condition
CEL p.Arg443Trp Uncertain significance ★★ same condition
CEL p.Asn37Ser Uncertain significance ★★ same condition
CEL p.Asp454Asn 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-arg116gln (accessed [today's date]).

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