Is CEBPA p.Pro23fs (c.68del) pathogenic?

CEBPA p.Pro23fs (c.68del) is classified Pathogenic in CEBPA (ClinVar, No assertion criteria, 2 submitters; last evaluated 2004-12-02). Very rare (popmax 8.37e-05%); Associated with acute myeloid leukemia.

What condition is associated with CEBPA p.Pro23fs (c.68del)?

CEBPA p.Pro23fs (c.68del) is associated with acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro23fs (c.68del) in the general population?

CEBPA p.Pro23fs (c.68del) is very rare (popmax 8.37e-05%) (gnomAD).

CEBPA p.Pro23fs

c.68del · rs137852728 · VCV17572

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.37e-05%)

Conditions

acute myeloid leukemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.074	GERP -2.3, phastCons 0.73

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.37e-05%

Overall 8.37e-05% 1/1,195,066 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: CEBPA
Protein: p.Pro23fs
Coding: c.68del
MANE Select: NM_004364
dbSNP: rs137852728
Type: Deletion
Location: chr19:33302347 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 23: the 'required to repress e2f1:tfdp1-mediated transcription, to inhibit cell cycle and to induce adipocyte differentiation' region; the 'disordered' region

Full CEBPA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

acute myeloid leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEBPA p.Pro23Arg Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro23Gln Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro23Ser Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro23Thr Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro23Leu Uncertain significance ★ ⚠ same residue
CEBPA p.Ala111fs Pathogenic ★★ same condition
CEBPA p.Gln83fs Pathogenic/Likely pathogenic ★★ same condition
CEBPA p.Glu89del 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/cebpa-p-pro23fs (accessed [today's date]).

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