Is CEBPA p.Ala40= (c.120G>T) pathogenic?

CEBPA p.Ala40= (c.120G>T) is classified Likely benign in CEBPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-05). Very rare (popmax 7.62e-05%); Associated with Inborn genetic diseases.

What condition is associated with CEBPA p.Ala40= (c.120G>T)?

CEBPA p.Ala40= (c.120G>T) is associated with Inborn genetic diseases, acute myeloid leukemia (ClinVar).

How common is CEBPA p.Ala40= (c.120G>T) in the general population?

CEBPA p.Ala40= (c.120G>T) is very rare (popmax 7.62e-05%) (gnomAD).

CEBPA p.Ala40=

c.120G>T · rs1555742292 · VCV456670

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 7.62e-05%)

Conditions

Inborn genetic diseases

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 2.1	GERP 0.035, phastCons 1
Overall
CADD	14.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.62e-05%

Overall 7.62e-05% 1/1,313,036 alleles · very 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.Ala40=
Coding: c.120G>T
MANE Select: NM_004364
dbSNP: rs1555742292
Type: single nucleotide variant
Location: chr19:33302295 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 40: 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.Ala40Val Uncertain significance ★★ ⚠ same residue
CEBPA p.Ala40Ser Uncertain significance ★ ⚠ same residue
CEBPA p.Ala40Thr 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
CEBPA p.Ala118Thr 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-ala40 (accessed [today's date]).

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