Is CEBPA p.Pro261Ser (c.781C>T) pathogenic?

CEBPA p.Pro261Ser (c.781C>T) is classified Uncertain significance in CEBPA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-20). AlphaMissense: likely benign (0.0808); Very rare (popmax 0.00189%, amr); Associated with acute myeloid leukemia.

What condition is associated with CEBPA p.Pro261Ser (c.781C>T)?

CEBPA p.Pro261Ser (c.781C>T) is associated with acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro261Ser (c.781C>T) in the general population?

CEBPA p.Pro261Ser (c.781C>T) is very rare (popmax 0.00189%, amr) (gnomAD).

What do computational predictors say about CEBPA p.Pro261Ser (c.781C>T)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

CEBPA p.Pro261Ser

c.781C>T · rs1263173603 · VCV854829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00189%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acute myeloid leukemia

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -2.3, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 384 bp · p 2.2e-07 · regional, not allelic
Overall
CADD	16.67	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00189% Admixed American · 1/52,952 alleles

Filtering AF 0.00051% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000373%

Overall 0.000851% 12/1,410,872 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00189%	52,952
European (non-Finnish)	0.00095%	105,216

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.Pro261Ser
Coding: c.781C>T
MANE Select: NM_004364
dbSNP: rs1263173603
Type: single nucleotide variant
Location: chr19:33301634 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 261: the 'interaction with foxo1' region; 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.Pro261Arg Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro261= Likely benign ★★ same residue
CEBPA p.Pro261Ala Uncertain significance ★ ⚠ 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

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-pro261ser (accessed [today's date]).

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