Is CEBPA p.Pro23Arg (c.68C>G) pathogenic?

CEBPA p.Pro23Arg (c.68C>G) is classified Uncertain significance in CEBPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-25). AlphaMissense: likely benign (0.1837); Ultra-rare (popmax 0.021%, mid); Associated with Inborn genetic diseases.

What condition is associated with CEBPA p.Pro23Arg (c.68C>G)?

CEBPA p.Pro23Arg (c.68C>G) is associated with Inborn genetic diseases, acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro23Arg (c.68C>G) in the general population?

CEBPA p.Pro23Arg (c.68C>G) is ultra-rare (popmax 0.021%, mid) (gnomAD).

What do computational predictors say about CEBPA p.Pro23Arg (c.68C>G)?

AlphaMissense predicts likely benign (score 0.1837) — an in-silico prediction, not a clinical call.

CEBPA p.Pro23Arg

c.68C>G · rs1308550194 · VCV2056621

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1837 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.021%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1837	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -7.41	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 1.8	GERP -2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 293 bp · p 0.38 · regional, not allelic
Overall
CADD	13.65	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 0.021% Middle Eastern · 1/4,752 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 6e-05%

Overall 0.000418% 5/1,195,256 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.021%	4,752
European (non-Finnish)	0.000381%	262,460

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.Pro23Arg
Coding: c.68C>G
MANE Select: NM_004364
dbSNP: rs1308550194
Type: single nucleotide variant
Location: chr19:33302347 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 23: 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.Pro23Gln Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro23Ser Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro23Thr Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro23Leu Uncertain significance ★ ⚠ same residue
CEBPA p.Pro23= Likely benign ★ same residue
CEBPA p.Pro23fs Pathogenic same residue
CEBPA p.Glu59Ter Pathogenic ★★ same condition
CEBPA c.-1C>A 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-pro23arg (accessed [today's date]).

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