Is CEBPE p.Asp41Asn (c.121G>A) pathogenic?

CEBPE p.Asp41Asn (c.121G>A) is classified Uncertain significance in CEBPE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.9373); Very rare (popmax 0.000593%, nfe); Associated with specific granule deficiency.

What condition is associated with CEBPE p.Asp41Asn (c.121G>A)?

CEBPE p.Asp41Asn (c.121G>A) is associated with specific granule deficiency (ClinVar).

How common is CEBPE p.Asp41Asn (c.121G>A) in the general population?

CEBPE p.Asp41Asn (c.121G>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CEBPE p.Asp41Asn (c.121G>A)?

AlphaMissense predicts likely pathogenic (score 0.9373) — an in-silico prediction, not a clinical call.

CEBPE p.Asp41Asn

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.121G>A · VCV4752893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9373 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

specific granule deficiency

Computational evidence

Protein change
AlphaMissense	0.9373	likely pathogenic
REVEL	0.384	indeterminate
SaProt	LLR -9.47	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,383 bp · p 0.39 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,976 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,812 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.Asp41Asn
Coding: c.121G>A
MANE Select: NM_001805
Type: single nucleotide variant
Location: chr14:23118971 (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 41: an α-helix

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.Asp41Gly 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-asp41asn (accessed [today's date]).

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