Is CEL p.Gln460Arg (c.1379A>G) pathogenic?

CEL p.Gln460Arg (c.1379A>G) is classified Uncertain significance in CEL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-25). Very rare (popmax 0.00195%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEL p.Gln460Arg (c.1379A>G)?

CEL p.Gln460Arg (c.1379A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEL p.Gln460Arg (c.1379A>G) in the general population?

CEL p.Gln460Arg (c.1379A>G) is very rare (popmax 0.00195%, nfe) (gnomAD).

CEL p.Gln460Arg

c.1379A>G · rs775977271 · VCV2570398

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.402	indeterminate
Splicing
SpliceAI	Δ0.30	donor gain · deltas
Constraint at this position
Conservation	phyloP 5.2	GERP -0.24, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 651 bp · p 0.0028 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,180,022 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00149% 24/1,613,962 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00195%	51,305
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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.Gln460Arg
Coding: c.1379A>G
MANE Select: NM_001807
dbSNP: rs775977271
Type: single nucleotide variant
Location: chr9:133070553 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 7 PDB
Residue 460: an α-helix

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

Similar variants

CEL p.Ala295Ser Uncertain significance ★★ same condition
CEL p.Ala548Glu Uncertain significance ★★ same condition
CEL p.Arg185Trp Uncertain significance ★★ same condition
CEL p.Arg443Trp Uncertain significance ★★ same condition
CEL p.Glu710Lys Uncertain significance ★★ same condition
CEL p.Gly147Ser Uncertain significance ★★ same condition
CEL p.His68Leu Uncertain significance ★★ same condition
CEL p.Ile89Val 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-gln460arg (accessed [today's date]).

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