VARS2 p.Ala129=
c.387C>T · VCV4684911
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00449%, 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 -0.44 | GERP -1.7 |
| Overall | ||
| CADD | 8.944 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00449%
European (non-Finnish) · 53/1,179,994 alleles
Filtering AF
0.0035%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00318%
Overall
0.00329%
53/1,613,244 alleles · very rare
exomes 53/1,460,960 · genomes 0/152,284 · joint denominator
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
- VARS2
- Protein
- p.Ala129=
- Coding
- c.387C>T
- MANE Select
- NM_020442
- Type
- single nucleotide variant
- Location
- chr6:30915748 (GRCh38)
- Structure
- AlphaFold pLDDT 88.12
- Residue 129
- the gst c-terminal domain
Similar variants
- VARS1 p.Arg1058Gln Likely pathogenic ★★ ⚠ same type
- VARS1 p.Arg1119Cys Pathogenic/Likely pathogenic ★★ same type
- VARS1 p.Arg1208Ter Pathogenic/Likely pathogenic ★★ same type
- VARS1 p.Gln1039Ter Likely pathogenic ★★ same type
- VARS1 p.Trp790Ter Pathogenic/Likely pathogenic ★★ same type
- VARS2 c.1480-2A>G Likely pathogenic ★★ same type
- VARS2 c.2467-2A>G Pathogenic/Likely pathogenic ★★ same type
- VARS2 p.Arg1002Ter 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/vars2-p-ala129 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown