Is CEBPE p.Pro27Ser (c.79C>T) pathogenic?

CEBPE p.Pro27Ser (c.79C>T) is classified Uncertain significance in CEBPE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-19). AlphaMissense: likely benign (0.078); Ultra-rare (popmax 0.0165%, mid).

How common is CEBPE p.Pro27Ser (c.79C>T) in the general population?

CEBPE p.Pro27Ser (c.79C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CEBPE p.Pro27Ser (c.79C>T)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

CEBPE p.Pro27Ser

c.79C>T · VCV3907648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -7.09	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 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,383 bp · p 0.39 · regional, not allelic
Overall
CADD	20.1	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000137% 2/1,461,220 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	8.48e-05%	1,179,933

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: CEBPE
Protein: p.Pro27Ser
Coding: c.79C>T
MANE Select: NM_001805
Type: single nucleotide variant
Location: chr14:23119013 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI 0.05 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 1 PDB
Residue 27: the 'disordered' region

Full CEBPE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEBPE p.Pro27= Likely benign ★ same residue
CEBPE p.Arg24Ter Pathogenic/Likely pathogenic ★★ same type
CEBPE p.Ala101Val Uncertain significance ★★ ⚠ same type
CEBPE p.Ala119Val Uncertain significance ★★ ⚠ same type
CEBPE p.Ala171Asp Uncertain significance ★★ ⚠ same type
CEBPE p.Ala44Thr Uncertain significance ★★ ⚠ same type
CEBPE p.Arg125Gln Uncertain significance ★★ ⚠ same type
CEBPE p.Arg135Gln Uncertain significance ★★ ⚠ same type

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/cebpe-p-pro27ser (accessed [today's date]).

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