Is CEBPA p.Pro129Ser (c.385C>T) pathogenic?

CEBPA p.Pro129Ser (c.385C>T) is classified Conflicting classifications of pathogenicity in CEBPA (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-09-12). AlphaMissense: likely benign (0.0847); Very rare (popmax 0.00463%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEBPA p.Pro129Ser (c.385C>T)?

CEBPA p.Pro129Ser (c.385C>T) is associated with Inborn genetic diseases, acute myeloid leukemia (ClinVar).

How common is CEBPA p.Pro129Ser (c.385C>T) in the general population?

CEBPA p.Pro129Ser (c.385C>T) is very rare (popmax 0.00463%, amr) (gnomAD).

What do computational predictors say about CEBPA p.Pro129Ser (c.385C>T)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

CEBPA p.Pro129Ser

c.385C>T · rs1328994773 · VCV456683

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00463%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -8.27	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 8	GERP -0.92, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 260 bp · p 0.13 · regional, not allelic
Overall
CADD	19.09	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00463% Admixed American · 1/21,586 alleles

Filtering AF 0.00243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.00296% 35/1,182,314 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00463%	21,586
East Asian	0.00379%	26,392
European (non-Finnish)	0.00335%	29,821
Remaining individualsnot grpmax-eligible	0.00241%	41,540

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.Pro129Ser
Coding: c.385C>T
MANE Select: NM_004364
dbSNP: rs1328994773
Type: single nucleotide variant
Location: chr19:33302030 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 2 PDB
Residue 129: the 'required to induce adipocyte differentiation' 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.Pro129His Uncertain significance ★★ ⚠ same residue
CEBPA p.Pro129= Likely benign ★ 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
CEBPA p.Ala118Val 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-pro129ser (accessed [today's date]).

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