Is CEL p.Leu118Arg (c.353T>G) pathogenic?

CEL p.Leu118Arg (c.353T>G) is classified Benign in CEL (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-06-24). Common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele; Associated with monogenic diabetes.

What condition is associated with CEL p.Leu118Arg (c.353T>G)?

CEL p.Leu118Arg (c.353T>G) is associated with monogenic diabetes, maturity-onset diabetes of the young type 8 (ClinVar).

CEL p.Leu118Arg

Q: How common is CEL p.Leu118Arg (c.353T>G) in the general population?

CEL p.Leu118Arg (c.353T>G) is common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.353T>G · rs113056079 · VCV128684

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

monogenic diabetes

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.479	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 0.66, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,610 bp · p 0.015 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.27% African / African-American · 3,945/74,890 alleles

Filtering AF 5.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.07%

Overall 0.318% 5,128/1,612,998 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.27%	19
Admixed American	0.696%	144
Middle Eastern	0.631%	158
Remaining individualsnot grpmax-eligible	0.507%	197
European (non-Finnish)	0.0333%	3,002
South Asian	0.0143%	7,005
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
Finnishnot grpmax-eligible	0.00474%	21,110

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.Leu118Arg
Coding: c.353T>G
MANE Select: NM_001807
dbSNP: rs113056079
Type: single nucleotide variant
Location: chr9:133065052 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 118: the 'heparin-binding' region; a β-strand

Full CEL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

monogenic diabetes — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: maturity-onset diabetes of the young type 8

Similar variants

CEL p.Leu118_Val120delinsArgProIle 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-leu118arg (accessed [today's date]).

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