VPS13B p.Ala2016=
c.6048G>A · rs200691718 · VCV1046333
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, afr)
Conditions
1
Cohen syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.92 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.63 | gain · loss 0.05 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -3.3 |
| Overall | ||
| CADD | 17.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/74,880 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00905%
Overall
0.00459%
74/1,613,124 alleles · ultra-rare
exomes 55/1,461,038 · genomes 19/152,086 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,349 |
| Middle Eastern | 0.0177% | 5,640 |
| South Asian | 0.00879% | 11,370 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,487 |
| Admixed American | 0.00667% | 14,997 |
| Finnishnot grpmax-eligible | 0.00626% | 15,968 |
| European (non-Finnish) | 0.00314% | 31,891 |
| East Asian | 0.00223% | 44,878 |
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.Ala2016=
- Coding
- c.6048G>A
- MANE Select
- NM_152564
- dbSNP
- rs200691718
- Type
- single nucleotide variant
- Location
- chr8:99699526 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Residue 2016
- 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); a UniProt-annotated variant site (in coh1; glycosylation is defective; accelerates differentiation of adipose cells); a UniProt-annotated variant site (in coh1; accelerates differentiation of adipose cells; response to insulin is abnormal)
Similar variants
- VPS13B p.Ala2016Val Uncertain significance ★ ⚠ 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
- VPS13B c.1843+1G>A 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-ala2016 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown