Is CEBPZ p.Thr352Pro (c.1054A>C) pathogenic?

CEBPZ p.Thr352Pro (c.1054A>C) is classified Uncertain significance in CEBPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). AlphaMissense: likely benign (0.2055); Very rare (popmax 0.000254%, nfe).

How common is CEBPZ p.Thr352Pro (c.1054A>C) in the general population?

CEBPZ p.Thr352Pro (c.1054A>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CEBPZ p.Thr352Pro (c.1054A>C)?

AlphaMissense predicts likely benign (score 0.2055) — an in-silico prediction, not a clinical call.

CEBPZ p.Thr352Pro

c.1054A>C · VCV3489941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2055	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -12.29	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 30 kb · p 4.9e-09 · regional, not allelic
Overall
CADD	21.9	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 0.000254% European (non-Finnish) · 3/1,180,026 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,890 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: CEBPZ
Protein: p.Thr352Pro
Coding: c.1054A>C
MANE Select: NM_005760
Type: single nucleotide variant
Location: chr2:37228139 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.34

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

Similar variants

CEBPZ p.Ala1008Thr Uncertain significance ★ ⚠ same type
CEBPZ p.Ala2Ser Uncertain significance ★ ⚠ same type
CEBPZ p.Ala2Val Uncertain significance ★ ⚠ same type
CEBPZ p.Ala365Val Uncertain significance ★ ⚠ same type
CEBPZ p.Ala369Ser Uncertain significance ★ ⚠ same type
CEBPZ p.Ala382Val Uncertain significance ★ ⚠ same type
CEBPZ p.Ala3Ser Uncertain significance ★ ⚠ same type
CEBPZ p.Ala3Val 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/cebpz-p-thr352pro (accessed [today's date]).

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