Is BACE2 p.Glu95Asp (c.285G>C) pathogenic?

BACE2 p.Glu95Asp (c.285G>C) is classified Uncertain significance in BACE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely benign (0.1568); Absent from gnomAD v4.1.

How common is BACE2 p.Glu95Asp (c.285G>C) in the general population?

BACE2 p.Glu95Asp (c.285G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BACE2 p.Glu95Asp (c.285G>C)?

AlphaMissense predicts likely benign (score 0.1568) — an in-silico prediction, not a clinical call.

BACE2 p.Glu95Asp

c.285G>C · rs2516878522 · VCV2324113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1568 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1568	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -6.21	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 3.5	GERP 0.23, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 69 kb · p 0.41 · regional, not allelic
Overall
CADD	26.0	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

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: BACE2
Protein: p.Glu95Asp
Coding: c.285G>C
MANE Select: NM_012105
dbSNP: rs2516878522
Type: single nucleotide variant
Location: chr21:41168548 (GRCh38)
Gene constraint: LOEUF 0.574 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 83.31 · 19 PDB
Residue 95: a β-strand; the peptidase a1 domain

Full BACE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BACE2 c.1135-10C>T Benign ★★ same type
BACE2 c.1304-8C>T Benign ★★ same type
BACE2 p.His56Tyr Benign ★★ ⚠ same type
BACE2 p.Ser88= Likely benign ★★ same type
BACE2 p.Ala200Gly Uncertain significance ★ ⚠ same type
BACE2 p.Ala25Val Uncertain significance ★ ⚠ same type
BACE2 p.Ala297Thr Uncertain significance ★ ⚠ same type
BACE2 p.Ala36Thr 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/bace2-p-glu95asp (accessed [today's date]).

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