VARS2 p.Pro311=
c.933C>T · VCV4798254
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
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 -3.1 | GERP -4 |
| Overall | ||
| CADD | 6.541 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,010 alleles
Filtering AF
0.00443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.00211%
33/1,566,794 alleles · ultra-rare
exomes 28/1,414,602 · genomes 5/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,010 |
| African / African-American | 0.00948% | 10,554 |
| Admixed American | 0.00565% | 17,694 |
| Remaining individualsnot grpmax-eligible | 0.00494% | 20,233 |
| European (non-Finnish) | 0.00164% | 60,807 |
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.Pro311=
- Coding
- c.933C>T
- MANE Select
- NM_020442
- Type
- single nucleotide variant
- Location
- chr6:30917754 (GRCh38)
- Structure
- AlphaFold pLDDT 88.12
Similar variants
- VARS2 p.Pro311Leu 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-pro311 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown