Is CEBPA p.Pro346= (c.1038A>G) pathogenic?

CEBPA p.Pro346= (c.1038A>G) is classified Conflicting classifications of pathogenicity in CEBPA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-23). Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEBPA p.Pro346= (c.1038A>G)?

CEBPA p.Pro346= (c.1038A>G) is associated with Inborn genetic diseases, acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro346= (c.1038A>G) in the general population?

CEBPA p.Pro346= (c.1038A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CEBPA p.Pro346=

c.1038A>G · VCV3606539

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 -3.7	GERP -3.4
Overall
CADD	3.048	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,372 alleles

Overall 6.87e-05% 1/1,455,434 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.Pro346=
Coding: c.1038A>G
MANE Select: NM_004364
Type: single nucleotide variant
Location: chr19:33301377 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 346: the 'interaction with foxo1' region

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.Pro346Arg Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro346Ser Uncertain significance ★ ⚠ same residue
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

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-pro346 (accessed [today's date]).

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