Is CEL p.Arg443Trp (c.1327C>T) pathogenic?

CEL p.Arg443Trp (c.1327C>T) is classified Uncertain significance in CEL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-25). Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Arg443Trp (c.1327C>T)?

CEL p.Arg443Trp (c.1327C>T) is associated with Inborn genetic diseases, maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Arg443Trp (c.1327C>T) in the general population?

CEL p.Arg443Trp (c.1327C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

CEL p.Arg443Trp

c.1327C>T · VCV3596562

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.561	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ1.00 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 0.75, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 651 bp · p 0.0028 · regional, not allelic
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000991% 16/1,613,812 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,238
European (non-Finnish)	0.000932%	107,271

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.Arg443Trp
Coding: c.1327C>T
MANE Select: NM_001807
Type: single nucleotide variant
Location: chr9:133070501 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: maturity-onset diabetes of the young type 8

Similar variants

CEL p.Arg443Gln 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.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-arg443trp (accessed [today's date]).

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