Is CEBPB p.Pro54Leu (c.161C>T) pathogenic?

CEBPB p.Pro54Leu (c.161C>T) is classified Uncertain significance in CEBPB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.1331); Very rare (popmax 0.000289%, nfe).

How common is CEBPB p.Pro54Leu (c.161C>T) in the general population?

CEBPB p.Pro54Leu (c.161C>T) is very rare (popmax 0.000289%, nfe) (gnomAD).

What do computational predictors say about CEBPB p.Pro54Leu (c.161C>T)?

AlphaMissense predicts likely benign (score 0.1331) — an in-silico prediction, not a clinical call.

CEBPB p.Pro54Leu

c.161C>T · VCV4225067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1331 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000289%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1331	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -8.77	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 2.4	GERP 1.3, phastCons 0.15
Regional constraint	o/e 1.02	unconstrained · MANE · 818 bp · p 0.69 · regional, not allelic
Overall
CADD	18.38	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 0.000289% European (non-Finnish) · 3/1,039,592 alleles

Filtering AF 7.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.1e-05%

Overall 0.000226% 3/1,324,576 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: CEBPB
Protein: p.Pro54Leu
Coding: c.161C>T
MANE Select: NM_005194
Type: single nucleotide variant
Location: chr20:50191194 (GRCh38)
Gene constraint: LOEUF 1.677 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 61.55 · 16 PDB
Residue 54: the 'required for myc transcriptional repression' region; the 'disordered' region

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

Similar variants

CEBPB p.Pro54Arg Uncertain significance ★ ⚠ same residue
CEBPB p.Ala103Thr Uncertain significance ★ ⚠ same type
CEBPB p.Ala103Val Uncertain significance ★ ⚠ same type
CEBPB p.Ala147Pro Uncertain significance ★ ⚠ same type
CEBPB p.Ala241Val Uncertain significance ★ ⚠ same type
CEBPB p.Ala247Val Uncertain significance ★ ⚠ same type
CEBPB p.Ala250Val Uncertain significance ★ ⚠ same type
CEBPB p.Ala253Thr 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/cebpb-p-pro54leu (accessed [today's date]).

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