Is CEBPA p.Pro127= (c.381C>A) pathogenic?

CEBPA p.Pro127= (c.381C>A) is classified Likely benign in CEBPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). Very rare (popmax 0.000105%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEBPA p.Pro127= (c.381C>A)?

CEBPA p.Pro127= (c.381C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CEBPA p.Pro127= (c.381C>A) in the general population?

CEBPA p.Pro127= (c.381C>A) is very rare (popmax 0.000105%, nfe) (gnomAD).

CEBPA p.Pro127=

c.381C>A · VCV4611045

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000105%, nfe)

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 0.28	GERP -2.4, phastCons 0.95
Overall
CADD	8.989	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000105% European (non-Finnish) · 1/955,750 alleles

Overall 9.65e-05% 1/1,036,280 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.Pro127=
Coding: c.381C>A
MANE Select: NM_004364
Type: single nucleotide variant
Location: chr19:33302034 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB

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.Pro127Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CEBPA p.Pro127His Uncertain significance ★ ⚠ same residue
CEBPA p.Pro127Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
CEBPA p.Pro127Thr 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

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-pro127 (accessed [today's date]).

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