Is BACE2 p.Val163= (c.489C>T) pathogenic?

BACE2 p.Val163= (c.489C>T) is classified Likely benign in BACE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Very rare (popmax 0.000593%, nfe).

How common is BACE2 p.Val163= (c.489C>T) in the general population?

BACE2 p.Val163= (c.489C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

BACE2 p.Val163=

c.489C>T · rs150489465 · VCV798000

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

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 0.2	GERP -1.2, phastCons 0.97
Overall
CADD	6.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,982 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,826 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: BACE2
Protein: p.Val163=
Coding: c.489C>T
MANE Select: NM_012105
dbSNP: rs150489465
Type: single nucleotide variant
Location: chr21:41237600 (GRCh38)
Gene constraint: LOEUF 0.574 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 83.31 · 19 PDB
Residue 163: 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-val163 (accessed [today's date]).

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