Is CEBPE p.Leu18= (c.54C>A) pathogenic?

CEBPE p.Leu18= (c.54C>A) is classified Likely benign in CEBPE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). Ultra-rare (popmax 0.0165%, mid); Associated with specific granule deficiency.

What condition is associated with CEBPE p.Leu18= (c.54C>A)?

CEBPE p.Leu18= (c.54C>A) is associated with specific granule deficiency (ClinVar).

How common is CEBPE p.Leu18= (c.54C>A) in the general population?

CEBPE p.Leu18= (c.54C>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CEBPE p.Leu18=

Q: How is Recurrent infections due to specific granule deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.54C>A · rs752307075 · VCV1607892

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

specific granule deficiency

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 -1.8	GERP -4.1
Overall
CADD	0.277	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000274% 4/1,460,218 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
African / African-American	0.00267%	37,481
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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: CEBPE
Protein: p.Leu18=
Coding: c.54C>A
MANE Select: NM_001805
dbSNP: rs752307075
Type: single nucleotide variant
Location: chr14:23119038 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI 0.05 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 1 PDB
Residue 18: the 'disordered' region

Full CEBPE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

specific granule deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Recurrent infections due to specific granule deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CEBPE p.Arg24Ter Pathogenic/Likely pathogenic ★★ same condition
CEBPE p.Ala101Val Uncertain significance ★★ ⚠ same condition
CEBPE p.Ala119Val Uncertain significance ★★ ⚠ same condition
CEBPE p.Ala171Asp Uncertain significance ★★ ⚠ same condition
CEBPE p.Ala44Thr Uncertain significance ★★ ⚠ same condition
CEBPE p.Arg125Gln Uncertain significance ★★ ⚠ same condition
CEBPE p.Arg135Gln Uncertain significance ★★ ⚠ same condition
CEBPE p.Arg167Cys 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/cebpe-p-leu18 (accessed [today's date]).

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