Is CEBPA p.Pro187= (c.561G>C) pathogenic?

CEBPA p.Pro187= (c.561G>C) is classified Benign/Likely benign in CEBPA (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-09). Rare (popmax 0.326%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with CEBPA p.Pro187= (c.561G>C)?

CEBPA p.Pro187= (c.561G>C) is associated with hereditary neoplastic syndrome, acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro187= (c.561G>C) in the general population?

CEBPA p.Pro187= (c.561G>C) is rare (popmax 0.326%, sas) (gnomAD).

CEBPA p.Pro187=

c.561G>C · rs538441046 · VCV415193

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.326%, sas)

Conditions

hereditary neoplastic syndrome

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 -2.2	GERP -2.1
Overall
CADD	11.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.326% South Asian · 172/52,692 alleles

Filtering AF 0.287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.271%

Overall 0.0347% 443/1,277,910 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.326%	306
Middle Eastern	0.186%	537
Ashkenazi Jewishnot grpmax-eligible	0.0939%	1,065
Remaining individualsnot grpmax-eligible	0.0419%	2,389
European (non-Finnish)	0.022%	4,551
Admixed American	0.0102%	9,820
East Asian	0.00395%	25,340
African / African-American	0.0032%	31,292
Finnishnot grpmax-eligible	0.00299%	33,410

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.Pro187=
Coding: c.561G>C
MANE Select: NM_004364
dbSNP: rs538441046
Type: single nucleotide variant
Location: chr19:33301854 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 187: 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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acute myeloid leukemia

Similar variants

CEBPA p.Pro187Gln Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro187_Pro189dup Uncertain significance ★★ same residue
CEBPA p.Pro187_Ser190delinsSerHisPro Uncertain significance ★★ same residue
CEBPA p.Pro187_Pro189del Conflicting classifications of pathogenicity ★ same residue
CEBPA p.Pro187fs Uncertain significance ★ same residue
CEBPA p.Pro187Leu Uncertain significance ★ ⚠ same residue
CEBPA p.Glu59Ter Pathogenic ★★ 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-pro187 (accessed [today's date]).

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