Is CPE p.Gln384= (c.1152A>G) pathogenic?

CPE p.Gln384= (c.1152A>G) is classified Likely benign in CPE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-15). Ultra-rare (popmax 0.0147%, afr); Associated with Inborn genetic diseases.

What condition is associated with CPE p.Gln384= (c.1152A>G)?

CPE p.Gln384= (c.1152A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CPE p.Gln384= (c.1152A>G) in the general population?

CPE p.Gln384= (c.1152A>G) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

CPE p.Gln384=

c.1152A>G · rs956945391 · VCV3032761

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.37	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.38	GERP -3, phastCons 0.001
Overall
CADD	1.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,934 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000805% 13/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,812
European (non-Finnish)	0.000169%	589,991

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: CPE
Protein: p.Gln384=
Coding: c.1152A>G
MANE Select: NM_001873
dbSNP: rs956945391
Type: single nucleotide variant
Location: chr4:165493209 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 90.83
Residue 384: a UniProt-annotated variant site (in bdvs)

Full CPE 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

Similar variants

CPE p.Gln384Ter Pathogenic ★ same residue
CPE p.Arg262Trp Uncertain significance ★★ ⚠ same condition
CPE p.Arg297Trp Uncertain significance ★★ ⚠ same condition
CPE p.Asp251Gly Uncertain significance ★★ ⚠ same condition
CPE p.Asp304Ala Uncertain significance ★★ ⚠ same condition
CPE p.Trp21Cys Uncertain significance ★★ ⚠ same condition
CPE p.Ala166Thr Uncertain significance ★ ⚠ same condition
CPE p.Ala166Val 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/cpe-p-gln384 (accessed [today's date]).

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