VARS1 p.Val581=
c.1743G>A · rs115320814 · VCV708919
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.63%, afr)
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 1.1 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 8.356 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.63%
African / African-American · 1,224/75,050 alleles
Filtering AF
1.55%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.52%
Overall
0.0864%
1,393/1,612,766 alleles · low-frequency
exomes 711/1,460,446 · genomes 682/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.63% | 61 |
| Admixed American | 0.138% | 723 |
| Remaining individualsnot grpmax-eligible | 0.115% | 868 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.0033% | 30,325 |
| European (non-Finnish) | 0.000848% | 117,992 |
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
- VARS1
- Protein
- p.Val581=
- Coding
- c.1743G>A
- MANE Select
- NM_006295
- dbSNP
- rs115320814
- Type
- single nucleotide variant
- Location
- chr6:31783115 (GRCh38)
- Gene constraint
- LOEUF 0.663 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.12
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/vars1-p-val581 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown