Is CEBPB p.Glu336Asp (c.1008G>T) pathogenic?

CEBPB p.Glu336Asp (c.1008G>T) is classified Uncertain significance in CEBPB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: ambiguous (0.5477); Very rare (popmax 0.00325%, nfe).

How common is CEBPB p.Glu336Asp (c.1008G>T) in the general population?

CEBPB p.Glu336Asp (c.1008G>T) is very rare (popmax 0.00325%, nfe) (gnomAD).

What do computational predictors say about CEBPB p.Glu336Asp (c.1008G>T)?

AlphaMissense predicts ambiguous (score 0.5477) — an in-silico prediction, not a clinical call.

CEBPB p.Glu336Asp

c.1008G>T · VCV3831245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5477 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00325%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5477	ambiguous
REVEL	0.076	moderately benign-leaning
SaProt	LLR -6.08	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 6.1	GERP -0.43, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 90 bp · p 0.64 · regional, not allelic
Overall
CADD	26.6	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 0.00325% European (non-Finnish) · 38/1,170,006 alleles

Filtering AF 0.00241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00211%

Overall 0.00264% 38/1,436,858 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.Glu336Asp
Coding: c.1008G>T
MANE Select: NM_005194
Type: single nucleotide variant
Location: chr20:50192041 (GRCh38)
Gene constraint: LOEUF 1.677 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 61.55 · 16 PDB

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-glu336asp (accessed [today's date]).

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