VPS53 p.Pro795=
c.2385C>T · rs893537097 · VCV2974697
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0168%, 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 0.009 | GERP -1.2 |
| Overall | ||
| CADD | 7.626 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0168%
Middle Eastern · 1/5,970 alleles
Filtering AF
0.0084%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00651%
Overall
0.00136%
21/1,544,774 alleles · ultra-rare
exomes 20/1,392,546 · genomes 1/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0168% | 5,970 |
| African / African-American | 0.0151% | 6,602 |
| East Asian | 0.00245% | 40,822 |
| South Asian | 0.0012% | 83,332 |
| European (non-Finnish) | 0.000612% | 163,499 |
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.Pro795=
- Coding
- c.2385C>T
- MANE Select
- NM_001128159
- dbSNP
- rs893537097
- Type
- single nucleotide variant
- Location
- chr17:519242 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.86
- Residue 795
- the 'disordered' region
Similar variants
- 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
- VPS53 p.Gly233Glu 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-pro795 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown