Is CEL p.Pro320Leu (c.959C>T) pathogenic?

CEL p.Pro320Leu (c.959C>T) is classified Uncertain significance in CEL (ClinVar, Single submitter, 1 submitter). Ultra-rare (popmax 0.0247%, eas); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Pro320Leu (c.959C>T)?

CEL p.Pro320Leu (c.959C>T) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Pro320Leu (c.959C>T) in the general population?

CEL p.Pro320Leu (c.959C>T) is ultra-rare (popmax 0.0247%, eas) (gnomAD).

How is MODY inherited?

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

CEL p.Pro320Leu

c.959C>T · VCV3382935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0247%, eas)

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	0.607	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.55 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 158 bp · p 2.1e-12 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0247% East Asian · 11/44,516 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00162% 26/1,606,954 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0247%	4,047
Ashkenazi Jewishnot grpmax-eligible	0.00678%	14,758
African / African-American	0.00544%	18,367
South Asian	0.00111%	89,712
European (non-Finnish)	0.000679%	147,170

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.Pro320Leu
Coding: c.959C>T
MANE Select: NM_001807
Type: single nucleotide variant
Location: chr9:133068735 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 320: 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 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
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-pro320leu (accessed [today's date]).

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