VPS53 p.Ser784=
c.2352C>T · rs1023247952 · VCV1207414
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0196%, afr)
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 6 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 11.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0196%
African / African-American · 14/71,494 alleles
Filtering AF
0.0118%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00945%
Overall
0.00105%
16/1,519,314 alleles · ultra-rare
exomes 13/1,367,094 · genomes 3/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0196% | 5,107 |
| Middle Eastern | 0.0171% | 5,838 |
| European (non-Finnish) | 8.82e-05% | 1,133,846 |
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.Ser784=
- Coding
- c.2352C>T
- MANE Select
- NM_001128159
- dbSNP
- rs1023247952
- Type
- single nucleotide variant
- Location
- chr17:519275 (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-ser784 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown