VPS13B p.Phe480=
c.1440C>T · rs141324814 · VCV193907
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 12 submitters
gnomAD v4.1
Rare
rare (popmax 0.171%, sas)
Conditions
2
Inborn genetic diseases
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 -0.087 | GERP -1.6, phastCons 0.003 |
| Overall | ||
| CADD | 8.628 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.171%
South Asian · 156/91,030 alleles
Filtering AF
0.149%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.141%
Overall
0.0442%
713/1,613,180 alleles · rare
exomes 673/1,461,018 · genomes 40/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.171% | 584 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,082 |
| European (non-Finnish) | 0.0424% | 2,359 |
| Admixed American | 0.03% | 3,330 |
| Middle Eastern | 0.0165% | 6,048 |
| African / African-American | 0.008% | 12,501 |
| Finnishnot grpmax-eligible | 0.00313% | 32,000 |
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
- VPS13B
- Protein
- p.Phe480=
- Coding
- c.1440C>T
- MANE Select
- NM_152564
- dbSNP
- rs141324814
- Type
- single nucleotide variant
- Location
- chr8:99135610 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Residue 480
- a UniProt-annotated variant site (in coh1); a UniProt-annotated variant site (in coh1; leads to an accumulation of liquid droplets and accelerates differentiation of adipose cells; response to insulin is abnormal)
Similar variants
- VPS13B p.Phe480Leu Uncertain significance ★ same residue
- VPS13B p.Phe480fs Pathogenic ★ same residue
- VPS13B c.10867+1G>A Likely pathogenic ★★ same condition
- VPS13B c.10868-2A>G Likely pathogenic ★★ same condition
- VPS13B c.11044+1G>A Pathogenic/Likely pathogenic ★★ same condition
- VPS13B c.11392+1G>T Likely pathogenic ★★ same condition
- VPS13B c.11496-2A>G Pathogenic ★★ same condition
- VPS13B c.11746-1G>A Pathogenic/Likely pathogenic ★★ same condition
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/vps13b-p-phe480 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown