Is CEBPE p.Lys185Thr (c.554A>C) pathogenic?

CEBPE p.Lys185Thr (c.554A>C) is classified Uncertain significance in CEBPE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-18). AlphaMissense: ambiguous (0.3842); Absent from gnomAD v4.1; Associated with specific granule deficiency.

What condition is associated with CEBPE p.Lys185Thr (c.554A>C)?

CEBPE p.Lys185Thr (c.554A>C) is associated with specific granule deficiency (ClinVar).

How common is CEBPE p.Lys185Thr (c.554A>C) in the general population?

CEBPE p.Lys185Thr (c.554A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEBPE p.Lys185Thr (c.554A>C)?

AlphaMissense predicts ambiguous (score 0.3842) — an in-silico prediction, not a clinical call.

CEBPE p.Lys185Thr

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.554A>C · rs2501818016 · VCV1986808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

specific granule deficiency

Computational evidence

Protein change
AlphaMissense	0.3842	ambiguous
REVEL	0.105	moderately benign-leaning
SaProt	LLR -6.06	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,383 bp · p 0.39 · regional, not allelic
Overall
CADD	19.68	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEBPE
Protein: p.Lys185Thr
Coding: c.554A>C
MANE Select: NM_001805
dbSNP: rs2501818016
Type: single nucleotide variant
Location: chr14:23117779 (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 185: 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.Lys185= Likely benign ★ 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-lys185thr (accessed [today's date]).

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