Is CEL p.Thr553= (c.1659C>G) pathogenic?

CEL p.Thr553= (c.1659C>G) is classified Benign in CEL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-07-21). Low-frequency (popmax 3.14%, afr); Associated with maturity-onset diabetes of the young type 8.

What condition is associated with CEL p.Thr553= (c.1659C>G)?

CEL p.Thr553= (c.1659C>G) is associated with maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Thr553= (c.1659C>G) in the general population?

CEL p.Thr553= (c.1659C>G) is low-frequency (popmax 3.14%, afr) (gnomAD).

How is MODY inherited?

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

CEL p.Thr553=

c.1659C>G · rs78256304 · VCV1288982

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.14%, afr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -2.6
Overall
CADD	0.027	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.14% African / African-American · 2,344/74,656 alleles

Filtering AF 3.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.99%

Overall 0.16% 2,565/1,607,670 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.14%	32
Remaining individualsnot grpmax-eligible	0.192%	520
Admixed American	0.119%	844
Middle Eastern	0.033%	3,030
South Asian	0.0033%	30,342
European (non-Finnish)	0.00212%	47,180

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.Thr553=
Coding: c.1659C>G
MANE Select: NM_001807
dbSNP: rs78256304
Type: single nucleotide variant
Location: chr9:133071161 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB

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.Thr553Ile 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-thr553 (accessed [today's date]).

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