Is CEBPE p.Arg24Ter (c.70C>T) pathogenic?

CEBPE p.Arg24Ter (c.70C>T) is classified Pathogenic/Likely pathogenic in CEBPE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-27). Very rare (popmax 0.0011%, sas); Associated with specific granule deficiency.

What condition is associated with CEBPE p.Arg24Ter (c.70C>T)?

CEBPE p.Arg24Ter (c.70C>T) is associated with specific granule deficiency (ClinVar).

How common is CEBPE p.Arg24Ter (c.70C>T) in the general population?

CEBPE p.Arg24Ter (c.70C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

CEBPE p.Arg24Ter

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.70C>T · rs1396196056 · VCV1324041

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

specific granule deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 2
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP -0.003, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,060 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000806% 13/1,612,940 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,474
South Asiangrpmax	0.0011%	91,060
European (non-Finnish)	0.000932%	107,262

Remaining individuals 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.Arg24Ter
Coding: c.70C>T
MANE Select: NM_001805
dbSNP: rs1396196056
Type: single nucleotide variant
Location: chr14:23119022 (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 24: 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.Arg24Gln Uncertain significance ★ ⚠ same residue
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-arg24ter (accessed [today's date]).

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