Is CPE p.Asp294Tyr (c.880G>T) pathogenic?

CPE p.Asp294Tyr (c.880G>T) is classified Uncertain significance in CPE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). AlphaMissense: likely benign (0.1835); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CPE p.Asp294Tyr (c.880G>T)?

CPE p.Asp294Tyr (c.880G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CPE p.Asp294Tyr (c.880G>T) in the general population?

CPE p.Asp294Tyr (c.880G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPE p.Asp294Tyr (c.880G>T)?

AlphaMissense predicts likely benign (score 0.1835) — an in-silico prediction, not a clinical call.

CPE p.Asp294Tyr

c.880G>T · VCV3496331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1835 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1835	likely benign
REVEL	0.342	indeterminate
SaProt	LLR -13.64	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 118 kb · p 0.00025 · regional, not allelic
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPE
Protein: p.Asp294Tyr
Coding: c.880G>T
MANE Select: NM_001873
Type: single nucleotide variant
Location: chr4:165484511 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 90.83
Residue 294: a UniProt-annotated variant site (in bdvs); the peptidase m14 domain

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.Asp294Gly Uncertain significance ⚠ 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.Gln384= Likely benign ★★ same condition
CPE p.Gln384Ter Pathogenic ★ 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-asp294tyr (accessed [today's date]).

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