Is CEBPA p.Pro43Ser (c.127C>T) pathogenic?

CEBPA p.Pro43Ser (c.127C>T) is classified Uncertain significance in CEBPA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-06). AlphaMissense: likely benign (0.0777); Absent from gnomAD v4.1; Associated with acute myeloid leukemia.

What condition is associated with CEBPA p.Pro43Ser (c.127C>T)?

CEBPA p.Pro43Ser (c.127C>T) is associated with acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro43Ser (c.127C>T) in the general population?

CEBPA p.Pro43Ser (c.127C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEBPA p.Pro43Ser (c.127C>T)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

CEBPA p.Pro43Ser

c.127C>T · rs2513333069 · VCV2122040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,474,268)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acute myeloid leukemia

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -8.67	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 8	GERP 0.031, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 293 bp · p 0.38 · regional, not allelic
Overall
CADD	20.4	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

No allele count reported in gnomAD v4.1 (AN 1,474,268). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CEBPA
Protein: p.Pro43Ser
Coding: c.127C>T
MANE Select: NM_004364
dbSNP: rs2513333069
Type: single nucleotide variant
Location: chr19:33302288 (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

acute myeloid leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEBPA p.Pro43= Likely benign ★★ same residue
CEBPA p.Pro43_Pro46del Uncertain significance ★ same residue
CEBPA p.Glu59Ter Pathogenic ★★ 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-pro43ser (accessed [today's date]).

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