BACE2 p.Ser88=
c.264T>A · rs376619639 · VCV755920
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0338%, 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 -10 | GERP -2.8 |
| Overall | ||
| CADD | 2.271 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0338%
European (non-Finnish) · 352/1,041,662 alleles
Filtering AF
0.0308%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0297%
Overall
0.0273%
368/1,346,766 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0338% | 2,959 |
| Remaining individualsnot grpmax-eligible | 0.0141% | 7,088 |
| African / African-American | 0.0136% | 7,380 |
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.Ser88=
- Coding
- c.264T>A
- MANE Select
- NM_012105
- dbSNP
- rs376619639
- Type
- single nucleotide variant
- Location
- chr21:41168527 (GRCh38)
- Gene constraint
- LOEUF 0.574 · pLI 0.73 (gnomAD)
- Structure
- AlphaFold pLDDT 83.31 · 19 PDB
- Residue 88
- a turn
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.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
- BACE2 p.Ala404Val 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-ser88 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown