Is CEL p.Ala548Glu (c.1643C>A) pathogenic?

CEL p.Ala548Glu (c.1643C>A) is classified Uncertain significance in CEL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-04). Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Ala548Glu (c.1643C>A)?

CEL p.Ala548Glu (c.1643C>A) is associated with Inborn genetic diseases, maturity-onset diabetes of the young type 8 (ClinVar).

How common is CEL p.Ala548Glu (c.1643C>A) in the general population?

CEL p.Ala548Glu (c.1643C>A) is very rare (popmax 0.00267%, afr) (gnomAD).

CEL p.Ala548Glu

c.1643C>A · rs529664291 · VCV2272038

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.044	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.066	GERP -2.7
Regional constraint	o/e 1.11	unconstrained · MANE · 642 bp · p 0.096 · regional, not allelic
Overall
CADD	2.976	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,810 alleles

Filtering AF 0.000764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00106% 17/1,608,490 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,405
European (non-Finnish)	0.00127%	78,637

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.Ala548Glu
Coding: c.1643C>A
MANE Select: NM_001807
dbSNP: rs529664291
Type: single nucleotide variant
Location: chr9:133071145 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 548: a turn

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.Ala548Thr Likely benign ★ same residue
CEL c.67-3C>A Uncertain significance ★★ same condition
CEL p.Ala295Ser 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-ala548glu (accessed [today's date]).

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