BACE2 p.Ala440=
c.1320A>C · VCV4645034
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00161%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.057 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -3.2 |
| Overall | ||
| CADD | 0.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00161%
European (non-Finnish) · 19/1,180,038 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00083%
Overall
0.00136%
22/1,614,064 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00161% | 62,107 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00133% | 74,926 |
| South Asian | 0.0011% | 91,094 |
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.Ala440=
- Coding
- c.1320A>C
- MANE Select
- NM_012105
- Type
- single nucleotide variant
- Location
- chr21:41275387 (GRCh38)
- Gene constraint
- LOEUF 0.574 · pLI 0.73 (gnomAD)
- Structure
- AlphaFold pLDDT 83.31 · 19 PDB
- Residue 440
- a disulfide bond; a β-strand
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-ala440 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown