VARS2 p.Pro323=
c.969C>T · rs148701242 · VCV1327281
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.609%, 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 -13 | GERP -4 |
| Overall | ||
| CADD | 0.056 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.609%
African / African-American · 448/73,530 alleles
Filtering AF
0.563%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.544%
Overall
0.033%
514/1,557,462 alleles · rare
exomes 233/1,405,166 · genomes 281/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.609% | 164 |
| Remaining individualsnot grpmax-eligible | 0.0497% | 2,013 |
| Admixed American | 0.0349% | 2,868 |
| Middle Eastern | 0.0334% | 2,994 |
| South Asian | 0.0119% | 8,430 |
| European (non-Finnish) | 0.000522% | 191,676 |
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.Pro323=
- Coding
- c.969C>T
- MANE Select
- NM_020442
- dbSNP
- rs148701242
- Type
- single nucleotide variant
- Location
- chr6:30917790 (GRCh38)
- Structure
- AlphaFold pLDDT 88.12
Similar variants
- VARS2 p.Pro323Ala Uncertain significance ★ ⚠ same residue
- 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
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-pro323 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown