Is CEBPA p.Arg291Pro (c.872G>C) pathogenic?

CEBPA p.Arg291Pro (c.872G>C) is classified Uncertain significance in CEBPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CEBPA p.Arg291Pro (c.872G>C)?

CEBPA p.Arg291Pro (c.872G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEBPA p.Arg291Pro (c.872G>C) in the general population?

CEBPA p.Arg291Pro (c.872G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEBPA p.Arg291Pro (c.872G>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

CEBPA p.Arg291Pro

c.872G>C · VCV3371947

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 4% in CEBPA
REVEL	0.672	pathogenic-leaning
SaProt	LLR -17.73	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 384 bp · p 2.2e-07 · regional, not allelic
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEBPA
Protein: p.Arg291Pro
Coding: c.872G>C
MANE Select: NM_004364
Type: single nucleotide variant
Location: chr19:33301543 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 291: the bzip domain; the 'interaction with foxo1' region; the 'basic motif' region; a DNA-binding region; an α-helix; 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

Similar variants

CEBPA p.Arg291His Uncertain significance ★★ ⚠ same residue
CEBPA p.Arg291Leu Uncertain significance ★ ⚠ same residue
CEBPA c.-1C>A Uncertain significance ★★ same condition
CEBPA c.-4C>G Uncertain significance ★★ same condition
CEBPA p.Ala118Thr Uncertain significance ★★ ⚠ same condition
CEBPA p.Ala154Val Uncertain significance ★★ ⚠ same condition
CEBPA p.Ala199Val Uncertain significance ★★ ⚠ same condition
CEBPA p.Ala238Val 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-arg291pro (accessed [today's date]).

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