Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 55.7%, eas) — too common for a highly-penetrant pathogenic allele
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 -11 | GERP -3.9 |
| Overall | ||
| CADD | 0.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
55.7%
East Asian · 24,911/44,700 alleles
Filtering AF
55.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 54.9%
Overall
19.6%
314,402/1,606,782 alleles · common
exomes 283,500/1,454,804 · genomes 30,902/151,978 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 55.7% | 2 |
| Admixed American | 40.4% | 2 |
| South Asian | 40% | 3 |
| Amishnot grpmax-eligible | 29.3% | 3 |
| Finnishnot grpmax-eligible | 24.2% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 22.3% | 4 |
| Remaining individualsnot grpmax-eligible | 22.3% | 4 |
| Middle Eastern | 19% | 5 |
| European (non-Finnish) | 15.5% | 6 |
| African / African-American | 13.9% | 7 |
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.Val552=
- Coding
- c.1656T>C
- MANE Select
- NM_020442
- dbSNP
- rs2074511
- Type
- single nucleotide variant
- Location
- chr6:30921612 (GRCh38)
- 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/vars2-p-val552 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown