Is CEBPA p.Val296= (c.888G>A) pathogenic?

CEBPA p.Val296= (c.888G>A) is classified Likely benign in CEBPA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-02). Ultra-rare (popmax 0.0233%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEBPA p.Val296= (c.888G>A)?

CEBPA p.Val296= (c.888G>A) is associated with Inborn genetic diseases, acute myeloid leukemia (ClinVar).

How common is CEBPA p.Val296= (c.888G>A) in the general population?

CEBPA p.Val296= (c.888G>A) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

CEBPA p.Val296=

c.888G>A · rs772999335 · VCV526822

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -1.9, phastCons 1
Overall
CADD	17.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0233% Admixed American · 14/60,000 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0013% 21/1,613,396 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,286
African / African-American	0.00133%	74,944
European (non-Finnish)	0.000509%	196,643

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.Val296=
Coding: c.888G>A
MANE Select: NM_004364
dbSNP: rs772999335
Type: single nucleotide variant
Location: chr19:33301527 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 296: the bzip domain; the 'interaction with foxo1' region; the 'basic motif' region; a DNA-binding region; an α-helix

Full CEBPA 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

Also linked: acute myeloid leukemia

Similar variants

CEBPA p.Glu59Ter Pathogenic ★★ same condition
CEBPA c.-1C>A Uncertain significance ★★ same condition
CEBPA c.-4C>G Uncertain significance ★★ same condition
CEBPA p.Ala113Ser Uncertain significance ★★ ⚠ same condition
CEBPA p.Ala118Thr Uncertain significance ★★ ⚠ same condition
CEBPA p.Ala118Val Uncertain significance ★★ ⚠ same condition
CEBPA p.Ala124Val Uncertain significance ★★ ⚠ same condition
CEBPA p.Ala154Val 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-val296 (accessed [today's date]).

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