VAMP2 p.Ile98=
c.294C>T · rs145487730 · VCV2647450
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.195%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP -0.97, phastCons 1 |
| Overall | ||
| CADD | 12.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.195%
African / African-American · 146/75,032 alleles
Filtering AF
0.169%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.159%
Overall
0.0121%
196/1,614,158 alleles · rare
exomes 93/1,461,866 · genomes 103/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.195% | 514 |
| Middle Eastern | 0.0495% | 2,021 |
| Admixed American | 0.02% | 5,002 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,209 |
| European (non-Finnish) | 0.00195% | 51,305 |
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.Ile98=
- Coding
- c.294C>T
- MANE Select
- NM_014232
- dbSNP
- rs145487730
- Type
- single nucleotide variant
- Location
- chr17:8161513 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.34 · 7 PDB
- Residue 98
- an α-helix; the 'required for interaction with sept8' region
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.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
- VAMP2 p.Arg66Pro 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-ile98 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown