VPS13B p.Phe2003=
c.6009T>C · rs1830220185 · VCV1100413
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 -0.1 | GERP -2.9, phastCons 0.001 |
| Overall | ||
| CADD | 4.744 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,838 alleles
Overall
6.2e-05%
1/1,613,576 alleles · very rare
exomes 1/1,461,304 · genomes 0/152,272 · joint denominator
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.Phe2003=
- Coding
- c.6009T>C
- MANE Select
- NM_152564
- dbSNP
- rs1830220185
- Type
- single nucleotide variant
- Location
- chr8:99661454 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Residue 2003
- 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.Phe2003fs Pathogenic/Likely 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
- 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-phe2003 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown