VPS13B p.Pro3653=
c.10959G>C · rs771022240 · VCV2823852
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
Cohen syndrome
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 -9.7 | GERP -4.3 |
| Overall | ||
| CADD | 0.119 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,872 alleles
Overall
0.000124%
2/1,614,150 alleles · very rare
exomes 2/1,461,872 · genomes 0/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,872 |
| South Asian | 0.0011% | 91,088 |
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.Pro3653=
- Coding
- c.10959G>C
- MANE Select
- NM_152564
- dbSNP
- rs771022240
- Type
- single nucleotide variant
- Location
- chr8:99859395 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Residue 3653
- 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); a UniProt-annotated variant site (in coh1; early endosomes are abnormal, lysosomes are enlarged and glycosylation is defective); a UniProt-annotated variant site (in coh1; disrupts protein localization to the perinuclear region; golgi stacks are fragmented, early endosomes are abnormal, lysosomes are enlarged and glycosylation is defective; leads to an accumulation of liquid droplets and accelerates differentiation of adipose cells; response to insulin is abnormal)
Similar variants
- VPS13B p.Pro3653Leu 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-pro3653 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown