Is CEL p.Ala722Val (c.2165C>T) pathogenic?

CEL p.Ala722Val (c.2165C>T) is classified Uncertain significance in CEL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-26). Very rare (popmax 0.00681%, amr); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Ala722Val (c.2165C>T)?

CEL p.Ala722Val (c.2165C>T) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Ala722Val (c.2165C>T) in the general population?

CEL p.Ala722Val (c.2165C>T) is very rare (popmax 0.00681%, amr) (gnomAD).

How is MODY inherited?

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

CEL p.Ala722Val

c.2165C>T · rs774058715 · VCV2215366

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00681%, 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	0.05	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -0.85
Regional constraint	o/e 1.11	unconstrained · MANE · 642 bp · p 0.096 · regional, not allelic
Overall
CADD	6.412	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00681% Admixed American · 4/58,746 alleles

Filtering AF 0.00229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000903% 14/1,550,104 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00681%	14,687
African / African-American	0.00426%	23,451
South Asian	0.00336%	29,791
European (non-Finnish)	0.000353%	282,997

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.Ala722Val
Coding: c.2165C>T
MANE Select: NM_001807
dbSNP: rs774058715
Type: single nucleotide variant
Location: chr9:133071667 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 722: the 'disordered' region; the '17 x 11 aa tandem repeats, glycodomain, o-linked (mucin type)' 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 p.Ala722Thr Uncertain significance ★ same residue
CEL p.Ala722= Likely benign ★ 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.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-ala722val (accessed [today's date]).

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