Is CEBPA p.Pro192Arg (c.575C>G) pathogenic?

CEBPA p.Pro192Arg (c.575C>G) is classified Uncertain significance in CEBPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-17). AlphaMissense: likely benign (0.1735); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CEBPA p.Pro192Arg (c.575C>G)?

CEBPA p.Pro192Arg (c.575C>G) is associated with Inborn genetic diseases, acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro192Arg (c.575C>G) in the general population?

CEBPA p.Pro192Arg (c.575C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEBPA p.Pro192Arg (c.575C>G)?

AlphaMissense predicts likely benign (score 0.1735) — an in-silico prediction, not a clinical call.

CEBPA p.Pro192Arg

c.575C>G · rs1247330890 · VCV1371773

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1735 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1735	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -11.40	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP -1.7, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 260 bp · p 0.13 · regional, not allelic
Overall
CADD	14.92	PHRED · no single calibrated threshold — expert panels disagree

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.Pro192Arg
Coding: c.575C>G
MANE Select: NM_004364
dbSNP: rs1247330890
Type: single nucleotide variant
Location: chr19:33301840 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 192: 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

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

Also linked: acute myeloid leukemia

Similar variants

CEBPA p.Pro192Leu Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro192= Likely benign ★★ same residue
CEBPA p.Pro192_His193insTyrPro Uncertain significance ★★ same residue
CEBPA p.Pro192_His205del 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

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-pro192arg (accessed [today's date]).

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