Is VPS13B p.Val2811fs (c.8430del) pathogenic?

VPS13B p.Val2811fs (c.8430del) is classified Pathogenic in VPS13B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). No gnomAD frequency available for this variant; Associated with Cohen syndrome.

What condition is associated with VPS13B p.Val2811fs (c.8430del)?

VPS13B p.Val2811fs (c.8430del) is associated with Cohen syndrome (ClinVar).

How common is VPS13B p.Val2811fs (c.8430del) in the general population?

VPS13B p.Val2811fs (c.8430del) is no gnomAD frequency available for this variant (gnomAD).

VPS13B p.Val2811fs

c.8430del · rs2130813174 · VCV1068499

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cohen syndrome

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 46 of 62
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: VPS13B
Protein: p.Val2811fs
Coding: c.8430del
MANE Select: NM_152564
dbSNP: rs2130813174
Type: Deletion
Location: chr8:99818518 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Residue 2811: 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)

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

Disease context

Cohen syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
VPS13B p.Asp3746fs 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-val2811fs (accessed [today's date]).

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