Is CEBPB p.Arg322Leu (c.965G>T) pathogenic?

CEBPB p.Arg322Leu (c.965G>T) is classified Uncertain significance in CEBPB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely pathogenic (0.9225); Absent from gnomAD v4.1.

How common is CEBPB p.Arg322Leu (c.965G>T) in the general population?

CEBPB p.Arg322Leu (c.965G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEBPB p.Arg322Leu (c.965G>T)?

AlphaMissense predicts likely pathogenic (score 0.9225) — an in-silico prediction, not a clinical call.

CEBPB p.Arg322Leu

c.965G>T · VCV4651780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9225 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9225	likely pathogenic
REVEL	0.495	indeterminate
SaProt	LLR -11.25	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP -2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 90 bp · p 0.64 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Arg322Leu
Coding: c.965G>T
MANE Select: NM_005194
Type: single nucleotide variant
Location: chr20:50191998 (GRCh38)
Gene constraint: LOEUF 1.677 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 61.55 · 16 PDB
Residue 322: the bzip domain; an α-helix

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-arg322leu (accessed [today's date]).

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