Is CEBPE p.Leu260Phe (c.778C>T) pathogenic?

CEBPE p.Leu260Phe (c.778C>T) is classified Uncertain significance in CEBPE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). AlphaMissense: likely pathogenic (0.9575); Very rare (popmax 0.000254%, nfe); Associated with specific granule deficiency.

What condition is associated with CEBPE p.Leu260Phe (c.778C>T)?

CEBPE p.Leu260Phe (c.778C>T) is associated with specific granule deficiency (ClinVar).

How common is CEBPE p.Leu260Phe (c.778C>T) in the general population?

CEBPE p.Leu260Phe (c.778C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CEBPE p.Leu260Phe (c.778C>T)?

AlphaMissense predicts likely pathogenic (score 0.9575) — an in-silico prediction, not a clinical call.

CEBPE p.Leu260Phe

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.778C>T · rs1420638415 · VCV855048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9575 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

specific granule deficiency

Computational evidence

Protein change
AlphaMissense	0.9575	likely pathogenic
REVEL	0.385	indeterminate
SaProt	LLR -10.72	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 170 bp · p 0.34 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,026 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,722 alleles · very rare

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.Leu260Phe
Coding: c.778C>T
MANE Select: NM_001805
dbSNP: rs1420638415
Type: single nucleotide variant
Location: chr14:23117555 (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 260: the bzip domain; 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.Leu260Arg Uncertain significance ★ ⚠ same residue
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

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-leu260phe (accessed [today's date]).

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