VPS33B p.Phe326=
c.978C>T · rs565539191 · VCV502345
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.95 | GERP -3.7 |
| Overall | ||
| CADD | 9.936 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,870 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000496%
8/1,614,144 alleles · very rare
exomes 7/1,461,892 · genomes 1/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,870 |
| South Asian | 0.0022% | 45,539 |
| Admixed American | 0.00167% | 60,006 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| African / African-American | 0.00133% | 75,026 |
| European (non-Finnish) | 0.000169% | 590,019 |
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
- VPS33B
- Protein
- p.Phe326=
- Coding
- c.978C>T
- MANE Select
- NM_018668
- dbSNP
- rs565539191
- Type
- single nucleotide variant
- Location
- chr15:91005746 (GRCh38)
- Gene constraint
- LOEUF 0.971 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.82
Similar variants
- VPS33B c.1030+1G>A Likely pathogenic ★★ same type
- VPS33B c.1225+5G>C Pathogenic/Likely pathogenic ★★ same type
- VPS33B c.239+5G>A Pathogenic/Likely pathogenic ★★ same type
- VPS33B c.240-1G>C Pathogenic/Likely pathogenic ★★ same type
- VPS33B c.403+2T>A Pathogenic ★★ same type
- VPS33B p.Arg107Ter Pathogenic/Likely pathogenic ★★ same type
- VPS33B p.Arg416Ter Pathogenic ★★ same type
- VPS33B p.Arg438Ter 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/vps33b-p-phe326 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown