Is CEBPA p.Pro189= (c.567C>T) pathogenic?

CEBPA p.Pro189= (c.567C>T) is classified Likely benign in CEBPA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-17). Very rare (popmax 9.74e-05%, nfe); Associated with acute myeloid leukemia.

What condition is associated with CEBPA p.Pro189= (c.567C>T)?

CEBPA p.Pro189= (c.567C>T) is associated with acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro189= (c.567C>T) in the general population?

CEBPA p.Pro189= (c.567C>T) is very rare (popmax 9.74e-05%, nfe) (gnomAD).

CEBPA p.Pro189=

c.567C>T · rs2145261321 · VCV1152824

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 9.74e-05%, nfe)

Conditions

acute myeloid leukemia

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 -1.5	GERP -1.5, phastCons 0.001
Overall
CADD	3.732	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.74e-05% European (non-Finnish) · 1/1,026,300 alleles

Overall 0.000172% 2/1,162,706 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0028%	35,668
European (non-Finnish)grpmax	9.74e-05%	1,026,300

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro189=
Coding: c.567C>T
MANE Select: NM_004364
dbSNP: rs2145261321
Type: single nucleotide variant
Location: chr19:33301848 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 189: the 'required to induce adipocyte differentiation' region; the 'disordered' region; the 'required to functionally cooperate with srebf1 in promoter activation' 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.Pro189Ser Uncertain significance ★ ⚠ same residue
CEBPA p.Pro189_Ser190insProProProSerHis Uncertain significance ★ same residue
CEBPA p.Pro189_Ser190insProSerHis Uncertain significance ★ same residue
CEBPA p.Pro189del Conflicting classifications of pathogenicity ★ same residue
CEBPA p.Pro189dup Conflicting classifications of pathogenicity ★ same residue
CEBPA p.Glu59Ter Pathogenic ★★ same condition
CEBPA p.Ala113Ser Uncertain significance ★★ ⚠ same condition
CEBPA p.Ala118Thr 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-pro189 (accessed [today's date]).

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