Is CEBPA p.Pro189Ser (c.565C>T) pathogenic?

CEBPA p.Pro189Ser (c.565C>T) is classified Uncertain significance in CEBPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely benign (0.0776); Very rare (popmax 0.000105%, nfe); Associated with acute myeloid leukemia.

What condition is associated with CEBPA p.Pro189Ser (c.565C>T)?

CEBPA p.Pro189Ser (c.565C>T) is associated with acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro189Ser (c.565C>T) in the general population?

CEBPA p.Pro189Ser (c.565C>T) is very rare (popmax 0.000105%, nfe) (gnomAD).

What do computational predictors say about CEBPA p.Pro189Ser (c.565C>T)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

CEBPA p.Pro189Ser

c.565C>T · VCV4730541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000105%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acute myeloid leukemia

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 260 bp · p 0.13 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000105% European (non-Finnish) · 1/955,250 alleles

Overall 9.39e-05% 1/1,064,466 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.Pro189Ser
Coding: c.565C>T
MANE Select: NM_004364
Type: single nucleotide variant
Location: chr19:33301850 (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.Pro189= Likely benign ★ 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-pro189ser (accessed [today's date]).

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