VMA22 p.Asp121=
c.363C>T · rs771683316 · VCV794114
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, 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 1.4 | phastCons 1 |
| Overall | ||
| CADD | 8.348 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00342%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0031%
Overall
0.00359%
58/1,613,640 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| European (non-Finnish) | 0.00441% | 22,689 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,233 |
| South Asian | 0.0022% | 45,492 |
| Finnishnot grpmax-eligible | 0.00156% | 64,014 |
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
- VMA22
- Protein
- p.Asp121=
- Coding
- c.363C>T
- MANE Select
- NM_032357
- dbSNP
- rs771683316
- Type
- single nucleotide variant
- Location
- chr2:130340975 (GRCh38)
- Gene constraint
- LOEUF 1.198 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.32
- Residue 121
- the 'disordered' region
Similar variants
- VMA22 p.Leu31Ser Pathogenic ★★ same type
- VMA22 p.Arg102Gln Uncertain significance ★★ ⚠ same type
- VMA22 p.Leu147Pro Uncertain significance ★★ ⚠ same type
- VMA22 p.Met49Lys Uncertain significance ★★ ⚠ same type
- VMA22 p.Ser72Arg Uncertain significance ★★ ⚠ same type
- VMA22 c.-402C>T Benign ★★ same type
- VMA22 p.Ala148= Benign/Likely benign ★★ same type
- VMA22 p.Ala180Val Likely benign ★★ 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/vma22-p-asp121 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown