VPS53 p.Arg820=
c.2460C>T · rs2543487418 · VCV2866015
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.74e-05%, nfe)
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 0.95 | GERP -4, phastCons 1 |
| Overall | ||
| CADD | 4.567 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.74e-05%
European (non-Finnish) · 1/1,144,120 alleles
Overall
6.48e-05%
1/1,544,172 alleles · very rare
exomes 1/1,391,798 · genomes 0/152,374 · joint denominator
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
- VPS53
- Protein
- p.Arg820=
- Coding
- c.2460C>T
- MANE Select
- NM_001128159
- dbSNP
- rs2543487418
- Type
- single nucleotide variant
- Location
- chr17:519167 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.86
- Residue 820
- the 'disordered' region
Similar variants
- VPS53 p.Arg820Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- VPS53 c.1556+5G>A Pathogenic/Likely pathogenic ★★ same type
- VPS53 p.Gln695Arg Pathogenic ★★ same type
- VPS53 p.Ala222Thr Uncertain significance ★★ ⚠ same type
- VPS53 p.Ala412Thr Uncertain significance ★★ ⚠ same type
- VPS53 p.Arg140Cys Uncertain significance ★★ ⚠ same type
- VPS53 p.Arg333Cys Uncertain significance ★★ ⚠ same type
- VPS53 p.Asp462Asn Uncertain significance ★★ ⚠ 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/vps53-p-arg820 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown