VPS50 p.Phe414=
c.1242T>C · VCV4533760
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0313%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.109 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 2.8 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 10.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0313%
Admixed American · 18/57,448 alleles
Filtering AF
0.0202%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0167%
Overall
0.00349%
56/1,602,862 alleles · ultra-rare
exomes 43/1,450,682 · genomes 13/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0313% | 3,192 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,049 |
| European (non-Finnish) | 0.00306% | 32,709 |
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
- VPS50
- Protein
- p.Phe414=
- Coding
- c.1242T>C
- MANE Select
- NM_017667
- Type
- single nucleotide variant
- Location
- chr7:93296816 (GRCh38)
- Gene constraint
- LOEUF 0.781 · pLI 0.11 (gnomAD)
- Structure
- AlphaFold pLDDT 71.19
Similar variants
- VPS50 p.Glu700Lys Uncertain significance ★★ ⚠ same type
- VPS50 p.Asn529Tyr Likely benign ★★ same type
- VPS50 p.Asn865Ser Benign ★★ same type
- VPS50 p.Pro896= Benign ★★ same type
- VPS50 c.2208-2A>G Likely pathogenic ★ same type
- VPS50 c.2464-1G>C Likely pathogenic ★ same type
- VPS50 p.Arg569Ter Likely pathogenic ★ same type
- VPS50 p.Gln575Ter Likely pathogenic ★ 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/vps50-p-phe414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown