Is CEBPB p.Pro254Arg (c.761C>G) pathogenic?

CEBPB p.Pro254Arg (c.761C>G) is classified Uncertain significance in CEBPB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: ambiguous (0.341); Absent from gnomAD v4.1.

How common is CEBPB p.Pro254Arg (c.761C>G) in the general population?

CEBPB p.Pro254Arg (c.761C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEBPB p.Pro254Arg (c.761C>G)?

AlphaMissense predicts ambiguous (score 0.341) — an in-silico prediction, not a clinical call.

CEBPB p.Pro254Arg

c.761C>G · rs2081580470 · VCV2325958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.341 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.341	ambiguous
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.25	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 0.75, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 818 bp · p 0.69 · regional, not allelic
Overall
CADD	21.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEBPB
Protein: p.Pro254Arg
Coding: c.761C>G
MANE Select: NM_005194
dbSNP: rs2081580470
Type: single nucleotide variant
Location: chr20:50191794 (GRCh38)
Gene constraint: LOEUF 1.677 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 61.55 · 16 PDB
Residue 254: the 'disordered' region

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

Similar variants

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
CEBPB p.Ala39Pro 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-pro254arg (accessed [today's date]).

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