VPS13B p.Pro1111=
c.3333G>A · rs367791771 · VCV1103332
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Conditions
1
Cohen syndrome
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 -0.86 | GERP -3.8 |
| Overall | ||
| CADD | 7.904 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00198%
32/1,613,766 alleles · ultra-rare
exomes 29/1,461,708 · genomes 3/152,058 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.00834% | 11,993 |
| European (non-Finnish) | 0.00195% | 51,300 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| African / African-American | 0.00134% | 74,882 |
| South Asian | 0.0011% | 91,074 |
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.Pro1111=
- Coding
- c.3333G>A
- MANE Select
- NM_152564
- dbSNP
- rs367791771
- Type
- single nucleotide variant
- Location
- chr8:99442523 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Residue 1111
- 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)
Similar variants
- VPS13B p.Pro1111Leu 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-pro1111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown