Is CEL p.Ile485Thr (c.1454T>C) pathogenic?

CEL p.Ile485Thr (c.1454T>C) is classified Benign/Likely benign in CEL (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-10-10). Low-frequency (popmax 3.29%, afr); Associated with monogenic diabetes.

What condition is associated with CEL p.Ile485Thr (c.1454T>C)?

CEL p.Ile485Thr (c.1454T>C) is associated with monogenic diabetes, maturity-onset diabetes of the young type 8, transient neonatal diabetes mellitus (ClinVar).

How common is CEL p.Ile485Thr (c.1454T>C) in the general population?

CEL p.Ile485Thr (c.1454T>C) is low-frequency (popmax 3.29%, afr) (gnomAD).

CEL p.Ile485Thr

c.1454T>C · rs77696629 · VCV393421

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.29%, afr)

Conditions

monogenic diabetes

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.615	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.83, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 651 bp · p 0.0028 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.29% African / African-American · 1,938/58,848 alleles

Filtering AF 3.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.12%

Overall 0.906% 13,022/1,436,658 alleles · low-frequency exomes 10,280/1,330,800 · genomes 2,742/105,858 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.29%	30
Middle Eastern	1.42%	70
South Asian	1.09%	92
Admixed American	1.09%	92
Amishnot grpmax-eligible	1.05%	95
Remaining individualsnot grpmax-eligible	0.869%	115
European (non-Finnish)	0.805%	124
Finnishnot grpmax-eligible	0.567%	176
Ashkenazi Jewishnot grpmax-eligible	0.526%	190
East Asian	0.248%	403

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.Ile485Thr
Coding: c.1454T>C
MANE Select: NM_001807
dbSNP: rs77696629
Type: single nucleotide variant
Location: chr9:133070628 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 485: an α-helix

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 transient neonatal diabetes mellitus

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-ile485thr (accessed [today's date]).

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