VAMP2 p.Ala72=
c.216G>A · VCV4933589
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
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 -6.2 | GERP -4.8 |
| Overall | ||
| CADD | 2.137 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/60,026 alleles
Filtering AF
0.00543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0038%
Overall
0.00223%
36/1,614,202 alleles · ultra-rare
exomes 31/1,461,872 · genomes 5/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,575 |
| African / African-American | 0.00533% | 18,760 |
| European (non-Finnish) | 0.00212% | 47,201 |
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
- VAMP2
- Protein
- p.Ala72=
- Coding
- c.216G>A
- MANE Select
- NM_014232
- Type
- single nucleotide variant
- Location
- chr17:8161674 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.34 · 7 PDB
- Residue 72
- the v-snare coiled-coil homology domain
Similar variants
- VAMP2 p.Ala74Val Uncertain significance ★★ ⚠ same type
- VAMP2 c.3-101G>T Likely benign ★★ same type
- VAMP2 c.334+12G>C Benign ★★ same type
- VAMP2 p.Ile98= Likely benign ★★ same type
- VAMP2 p.Leu54= Likely benign ★★ same type
- VAMP2 c.2+2T>C Likely pathogenic ★ same type
- VAMP2 p.Arg56Leu Likely pathogenic ★ same type
- VAMP2 p.Arg56Ter Pathogenic ★ 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/vamp2-p-ala72 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown