VPS53 p.Asp62=
c.186C>T · rs754421324 · VCV2903686
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0012%, sas)
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 -2.1 | GERP -3.2 |
| Overall | ||
| CADD | 5.305 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0012%
South Asian · 1/83,652 alleles
Filtering AF
0.00055%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000434%
Overall
0.000827%
13/1,571,638 alleles · very rare
exomes 11/1,419,634 · genomes 2/152,004 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0012% | 83,652 |
| European (non-Finnish) | 0.00103% | 96,946 |
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.Asp62=
- Coding
- c.186C>T
- MANE Select
- NM_001128159
- dbSNP
- rs754421324
- Type
- single nucleotide variant
- Location
- chr17:699363 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.86
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-asp62 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown