Is CEL p.Ser720Phe (c.2159C>T) pathogenic?

CEL p.Ser720Phe (c.2159C>T) is classified Uncertain significance in CEL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). Very rare (popmax 8.66e-05%, nfe); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Ser720Phe (c.2159C>T)?

CEL p.Ser720Phe (c.2159C>T) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Ser720Phe (c.2159C>T) in the general population?

CEL p.Ser720Phe (c.2159C>T) is very rare (popmax 8.66e-05%, nfe) (gnomAD).

How is MODY inherited?

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

CEL p.Ser720Phe

c.2159C>T · VCV3596591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.66e-05%, nfe)

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	0.121	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP -0.79
Regional constraint	o/e 1.11	unconstrained · MANE · 642 bp · p 0.096 · regional, not allelic
Overall
CADD	15.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.66e-05% European (non-Finnish) · 1/1,154,684 alleles

Overall 6.34e-05% 1/1,577,536 alleles · very rare exomes 1/1,433,300 · genomes 0/144,236 · joint denominator

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.Ser720Phe
Coding: c.2159C>T
MANE Select: NM_001807
Type: single nucleotide variant
Location: chr9:133071661 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 720: 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.Ser720= 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.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-ser720phe (accessed [today's date]).

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