Is CEBPA p.Pro43= (c.129C>T) pathogenic?

CEBPA p.Pro43= (c.129C>T) is classified Likely benign in CEBPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-04). Very rare (popmax 0.000451%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEBPA p.Pro43= (c.129C>T)?

CEBPA p.Pro43= (c.129C>T) is associated with Inborn genetic diseases, acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro43= (c.129C>T) in the general population?

CEBPA p.Pro43= (c.129C>T) is very rare (popmax 0.000451%, nfe) (gnomAD).

CEBPA p.Pro43=

c.129C>T · rs1060504476 · VCV1152688

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000451%, 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 -2.3
Overall
CADD	7.204	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000451% European (non-Finnish) · 5/1,108,746 alleles

Filtering AF 0.000132% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.6e-05%

Overall 0.000453% 6/1,323,666 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00178%	56,170
European (non-Finnish)grpmax	0.000451%	221,749

Remaining individuals 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.Pro43=
Coding: c.129C>T
MANE Select: NM_004364
dbSNP: rs1060504476
Type: single nucleotide variant
Location: chr19:33302286 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 43: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acute myeloid leukemia

Similar variants

CEBPA p.Pro43Ser Uncertain significance ★ ⚠ same residue
CEBPA p.Pro43_Pro46del 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-pro43 (accessed [today's date]).

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