VPS53 p.Val751=
c.2253G>A · rs377274469 · VCV1223201
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.684%, 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 1.5 | GERP 0.044, phastCons 1 |
| Overall | ||
| CADD | 9.054 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.684%
South Asian · 575/84,052 alleles
Filtering AF
0.638%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.619%
Overall
0.0467%
724/1,551,588 alleles · rare
exomes 683/1,399,376 · genomes 41/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.684% | 146 |
| East Asian | 0.066% | 1,515 |
| Remaining individualsnot grpmax-eligible | 0.0582% | 1,718 |
| Middle Eastern | 0.0334% | 2,994 |
| Admixed American | 0.00784% | 12,747 |
| European (non-Finnish) | 0.00697% | 14,337 |
| Finnishnot grpmax-eligible | 0.00167% | 59,888 |
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.Val751=
- Coding
- c.2253G>A
- MANE Select
- NM_001128159
- dbSNP
- rs377274469
- Type
- single nucleotide variant
- Location
- chr17:519901 (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 p.Val751Met Uncertain significance ★ ⚠ 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-val751 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown