Is BACE2 p.Asp364= (c.1092C>T) pathogenic?

BACE2 p.Asp364= (c.1092C>T) is classified Benign in BACE2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-30). Common (popmax 71.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with BACE2-related disorder.

What condition is associated with BACE2 p.Asp364= (c.1092C>T)?

BACE2 p.Asp364= (c.1092C>T) is associated with BACE2-related disorder (ClinVar).

BACE2 p.Asp364=

Q: How common is BACE2 p.Asp364= (c.1092C>T) in the general population?

BACE2 p.Asp364= (c.1092C>T) is common (popmax 71.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1092C>T · rs1046210 · VCV3060688

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 71.9%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

BACE2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -4.2
Overall
CADD	2.863	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 71.9% East Asian · 32,245/44,868 alleles

Filtering AF 71.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 70.9%

Overall 40.5% 652,985/1,613,088 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	71.9%	1
Admixed American	57.2%	2
South Asian	54.8%	2
Middle Eastern	48.6%	2
Remaining individualsnot grpmax-eligible	41.4%	2
Amishnot grpmax-eligible	40.4%	2
Finnishnot grpmax-eligible	40.2%	2
Ashkenazi Jewishnot grpmax-eligible	39.5%	3
European (non-Finnish)	39.1%	3
African / African-American	11.9%	8

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: BACE2
Protein: p.Asp364=
Coding: c.1092C>T
MANE Select: NM_012105
dbSNP: rs1046210
Type: single nucleotide variant
Location: chr21:41250859 (GRCh38)
Gene constraint: LOEUF 0.574 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 83.31 · 19 PDB
Residue 364: a disulfide bond; the peptidase a1 domain

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

Disease context

BACE2-related disorder

Similar variants

BACE2 c.748-10C>T Benign same condition
BACE2 p.Ala37= Benign same condition
BACE2 p.Ala460Thr Likely benign same condition
PLAC4 n.5627C>T Likely benign same condition
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

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-asp364 (accessed [today's date]).

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