Is CEBPZ p.Leu208Phe (c.622C>T) pathogenic?

CEBPZ p.Leu208Phe (c.622C>T) is classified Uncertain significance in CEBPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). AlphaMissense: likely benign (0.1791); Ultra-rare (popmax 0.0187%, afr).

How common is CEBPZ p.Leu208Phe (c.622C>T) in the general population?

CEBPZ p.Leu208Phe (c.622C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about CEBPZ p.Leu208Phe (c.622C>T)?

AlphaMissense predicts likely benign (score 0.1791) — an in-silico prediction, not a clinical call.

CEBPZ p.Leu208Phe

c.622C>T · VCV3831255

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1791 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1791	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -7.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -0.61, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 30 kb · p 4.9e-09 · regional, not allelic
Overall
CADD	18.6	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 0.0187% African / African-American · 14/74,934 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00112% 18/1,614,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,352
Admixed American	0.005%	20,001
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Leu208Phe
Coding: c.622C>T
MANE Select: NM_005760
Type: single nucleotide variant
Location: chr2:37228571 (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-leu208phe (accessed [today's date]).

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