Is CEBPE p.Pro82Leu (c.245C>T) pathogenic?

CEBPE p.Pro82Leu (c.245C>T) is classified Uncertain significance in CEBPE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-29). AlphaMissense: likely benign (0.1803); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with CEBPE p.Pro82Leu (c.245C>T)?

CEBPE p.Pro82Leu (c.245C>T) is associated with Inborn genetic diseases, specific granule deficiency (ClinVar).

How common is CEBPE p.Pro82Leu (c.245C>T) in the general population?

CEBPE p.Pro82Leu (c.245C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CEBPE p.Pro82Leu (c.245C>T)?

AlphaMissense predicts likely benign (score 0.1803) — an in-silico prediction, not a clinical call.

CEBPE p.Pro82Leu

c.245C>T · rs372292172 · VCV1411777

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1803	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -7.45	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 6.5	GERP 0.073, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,383 bp · p 0.39 · regional, not allelic
Overall
CADD	23.0	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 0.004% African / African-American · 3/75,032 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000753% 11/1,461,714 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,011
South Asian	0.0022%	45,543
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	0.000339%	294,989

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: CEBPE
Protein: p.Pro82Leu
Coding: c.245C>T
MANE Select: NM_001805
dbSNP: rs372292172
Type: single nucleotide variant
Location: chr14:23118847 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI 0.05 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 1 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: specific granule deficiency

Similar variants

CEBPE p.Pro82Ser Uncertain significance ★ ⚠ same residue
CEBPE p.Arg24Ter Pathogenic/Likely pathogenic ★★ same condition
CEBPE p.Ala101Val Uncertain significance ★★ ⚠ same condition
CEBPE p.Ala119Val Uncertain significance ★★ ⚠ same condition
CEBPE p.Ala171Asp Uncertain significance ★★ ⚠ same condition
CEBPE p.Ala44Thr Uncertain significance ★★ ⚠ same condition
CEBPE p.Arg125Gln Uncertain significance ★★ ⚠ same condition
CEBPE p.Arg135Gln Uncertain significance ★★ ⚠ same condition

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/cebpe-p-pro82leu (accessed [today's date]).

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