Is CEBPA p.Pro222= (c.666C>T) pathogenic?

CEBPA p.Pro222= (c.666C>T) is classified Likely benign in CEBPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-22). Ultra-rare (popmax 0.0395%, sas); Associated with acute myeloid leukemia.

What condition is associated with CEBPA p.Pro222= (c.666C>T)?

CEBPA p.Pro222= (c.666C>T) is associated with acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro222= (c.666C>T) in the general population?

CEBPA p.Pro222= (c.666C>T) is ultra-rare (popmax 0.0395%, sas) (gnomAD).

CEBPA p.Pro222=

c.666C>T · rs1184004794 · VCV1157238

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0395%, sas)

Conditions

acute myeloid leukemia

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 -3.2	GERP -2.5
Overall
CADD	8.997	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0395% South Asian · 10/25,316 alleles

Filtering AF 0.0214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0162%

Overall 0.000857% 10/1,167,300 alleles · ultra-rare

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.Pro222=
Coding: c.666C>T
MANE Select: NM_004364
dbSNP: rs1184004794
Type: single nucleotide variant
Location: chr19:33301749 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 222: 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.Pro222Leu Uncertain significance ★ ⚠ same residue
CEBPA p.Pro222Ser Conflicting classifications of pathogenicity ★ ⚠ 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-pro222 (accessed [today's date]).

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