Is CEBPE p.Arg249= (c.747C>T) pathogenic?

CEBPE p.Arg249= (c.747C>T) is classified Benign/Likely benign in CEBPE (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.79%, nfe); Associated with specific granule deficiency.

What condition is associated with CEBPE p.Arg249= (c.747C>T)?

CEBPE p.Arg249= (c.747C>T) is associated with specific granule deficiency (ClinVar).

How common is CEBPE p.Arg249= (c.747C>T) in the general population?

CEBPE p.Arg249= (c.747C>T) is low-frequency (popmax 1.79%, nfe) (gnomAD).

CEBPE p.Arg249=

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.747C>T · rs55722931 · VCV461468

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.79%, nfe)

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 -7.3	GERP -4.8
Overall
CADD	2.882	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.79% European (non-Finnish) · 21,142/1,180,032 alleles

Filtering AF 1.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.76%

Overall 1.67% 26,995/1,614,098 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	5.18%	19
Finnishnot grpmax-eligible	2.66%	38
European (non-Finnish)grpmax	1.79%	56
Remaining individualsnot grpmax-eligible	1.76%	57
Middle Eastern	1.37%	73
South Asian	0.946%	106
Admixed American	0.646%	155
African / African-American	0.249%	401
Amishnot grpmax-eligible	0.11%	910

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg249=
Coding: c.747C>T
MANE Select: NM_001805
dbSNP: rs55722931
Type: single nucleotide variant
Location: chr14:23117586 (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 249: the bzip domain; a UniProt-annotated variant site (in sgd1; decreased function in positive regulation of dna-templated transcription; loss of interaction with gata1; decreased interaction with spi1; no effect on localization to nucleus; no effect on dna binding; no effect on dimerization); a UniProt-annotated variant site (in sgd1)

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-arg249 (accessed [today's date]).

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