Is CEBPZ p.Asp697Asn (c.2089G>A) pathogenic?

CEBPZ p.Asp697Asn (c.2089G>A) is classified Uncertain significance in CEBPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). AlphaMissense: likely benign (0.1276); Very rare (popmax 0.00224%, eas).

How common is CEBPZ p.Asp697Asn (c.2089G>A) in the general population?

CEBPZ p.Asp697Asn (c.2089G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about CEBPZ p.Asp697Asn (c.2089G>A)?

AlphaMissense predicts likely benign (score 0.1276) — an in-silico prediction, not a clinical call.

CEBPZ p.Asp697Asn

c.2089G>A · rs527993550 · VCV2281099

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1276 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1276	likely benign
REVEL	0.451	indeterminate
SaProt	LLR -8.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 30 kb · p 4.9e-09 · regional, not allelic
Overall
CADD	25.8	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 0.00224% East Asian · 1/44,572 alleles

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

Overall 0.000438% 7/1,596,710 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,572
Remaining individualsnot grpmax-eligible	0.00162%	61,904
African / African-American	0.00134%	74,420
South Asian	0.00113%	88,488
European (non-Finnish)	0.000257%	389,576

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.Asp697Asn
Coding: c.2089G>A
MANE Select: NM_005760
dbSNP: rs527993550
Type: single nucleotide variant
Location: chr2:37220450 (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-asp697asn (accessed [today's date]).

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