Is CEBPE p.Ala171Asp (c.512C>A) pathogenic?

CEBPE p.Ala171Asp (c.512C>A) is classified Uncertain significance in CEBPE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-05). AlphaMissense: ambiguous (0.4173); Very rare (popmax 0.000342%, nfe); Associated with specific granule deficiency.

What condition is associated with CEBPE p.Ala171Asp (c.512C>A)?

CEBPE p.Ala171Asp (c.512C>A) is associated with specific granule deficiency (ClinVar).

How common is CEBPE p.Ala171Asp (c.512C>A) in the general population?

CEBPE p.Ala171Asp (c.512C>A) is very rare (popmax 0.000342%, nfe) (gnomAD).

What do computational predictors say about CEBPE p.Ala171Asp (c.512C>A)?

AlphaMissense predicts ambiguous (score 0.4173) — an in-silico prediction, not a clinical call.

CEBPE p.Ala171Asp

Q: How is Recurrent infections due to specific granule deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.512C>A · rs751972931 · VCV2085203

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4173 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000342%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

specific granule deficiency

Computational evidence

Protein change
AlphaMissense	0.4173	ambiguous
REVEL	0.079	moderately benign-leaning
SaProt	LLR -6.65	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 6.3	GERP 2.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,383 bp · p 0.39 · regional, not allelic
Overall
CADD	21.8	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 0.000342% European (non-Finnish) · 4/1,171,046 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000277% 4/1,443,886 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: CEBPE
Protein: p.Ala171Asp
Coding: c.512C>A
MANE Select: NM_001805
dbSNP: rs751972931
Type: single nucleotide variant
Location: chr14:23117821 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI 0.05 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 1 PDB
Residue 171: a UniProt-annotated variant site (in sgd1)

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

Disease context

specific granule deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Recurrent infections due to specific granule deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CEBPE p.Ala171Thr Uncertain significance ★ ⚠ same residue
CEBPE p.Ala171Gly 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.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-ala171asp (accessed [today's date]).

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