Is VPS13B p.Phe2003fs (c.6009del) pathogenic?

VPS13B p.Phe2003fs (c.6009del) is classified Pathogenic/Likely pathogenic in VPS13B (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-28). Very rare (popmax 0.000932%, nfe); Associated with VPS13B-related disorder.

What condition is associated with VPS13B p.Phe2003fs (c.6009del)?

VPS13B p.Phe2003fs (c.6009del) is associated with VPS13B-related disorder, Cohen syndrome (ClinVar).

How common is VPS13B p.Phe2003fs (c.6009del) in the general population?

VPS13B p.Phe2003fs (c.6009del) is very rare (popmax 0.000932%, nfe) (gnomAD).

VPS13B p.Phe2003fs

c.6009del · rs1357171752 · VCV437257

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Conditions

VPS13B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 35 of 62
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.007	GERP 0.93, phastCons 0.64
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,798 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,406 alleles · very rare exomes 9/1,461,304 · genomes 2/152,102 · 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.Phe2003fs
Coding: c.6009del
MANE Select: NM_152564
dbSNP: rs1357171752
Type: Deletion
Location: chr8:99661452 (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)

Full VPS13B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

VPS13B-related disorder

Also linked: Cohen syndrome

Similar variants

VPS13B p.Phe2003= Likely benign ★ same residue
VPS13B p.Ala2763fs Pathogenic ★★ same condition
VPS13B p.Ala3695fs Pathogenic/Likely pathogenic ★★ same condition
VPS13B p.Arg1779fs Pathogenic/Likely pathogenic ★★ same condition
VPS13B p.Arg2326_Ile2327insTer Pathogenic/Likely pathogenic ★★ same condition
VPS13B p.Arg3840fs Pathogenic/Likely pathogenic ★★ same condition
VPS13B p.Asn2406fs Pathogenic/Likely pathogenic ★★ same condition
VPS13B p.Asp306fs 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-phe2003fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown