Is CEBPE p.Ser248Arg (c.742A>C) pathogenic?

CEBPE p.Ser248Arg (c.742A>C) is classified Uncertain significance in CEBPE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely pathogenic (0.6519); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CEBPE p.Ser248Arg (c.742A>C)?

CEBPE p.Ser248Arg (c.742A>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEBPE p.Ser248Arg (c.742A>C) in the general population?

CEBPE p.Ser248Arg (c.742A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEBPE p.Ser248Arg (c.742A>C)?

AlphaMissense predicts likely pathogenic (score 0.6519) — an in-silico prediction, not a clinical call.

CEBPE p.Ser248Arg

c.742A>C · rs2501817449 · VCV2329723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6519 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6519	likely pathogenic
REVEL	0.049	moderately benign-leaning
SaProt	LLR -2.93	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.3, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 170 bp · p 0.34 · regional, not allelic
Overall
CADD	19.42	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.Ser248Arg
Coding: c.742A>C
MANE Select: NM_001805
dbSNP: rs2501817449
Type: single nucleotide variant
Location: chr14:23117591 (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 248: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEBPE p.Ala119Val Uncertain significance ★★ ⚠ same condition
CEBPE p.Arg135Gln Uncertain significance ★★ ⚠ same condition
CEBPE p.Arg265Cys Uncertain significance ★★ same condition
CEBPE p.Glu19Gln Uncertain significance ★★ ⚠ same condition
CEBPE p.Gly28Arg Uncertain significance ★★ ⚠ same condition
CEBPE p.Gly49Arg Uncertain significance ★★ ⚠ same condition
CEBPE p.His194Asn Uncertain significance ★★ ⚠ same condition
CEBPE p.Leu173Val 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-ser248arg (accessed [today's date]).

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