VPS33B p.Ser392=
c.1176G>A · VCV3618690
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00878%, 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 -3.4 | GERP -3.6 |
| Overall | ||
| CADD | 6.053 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00878%
South Asian · 8/91,088 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.00136%
22/1,614,076 alleles · very rare
exomes 20/1,461,888 · genomes 2/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00878% | 11,386 |
| African / African-American | 0.00267% | 37,461 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish) | 0.000932% | 107,277 |
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.Ser392=
- Coding
- c.1176G>A
- MANE Select
- NM_018668
- Type
- single nucleotide variant
- Location
- chr15:91004926 (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-ser392 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown