Is VPS13B p.Ser247= (c.741C>T) pathogenic?

VPS13B p.Ser247= (c.741C>T) is classified Likely benign in VPS13B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). Absent from gnomAD v4.1; Associated with Cohen syndrome.

What condition is associated with VPS13B p.Ser247= (c.741C>T)?

VPS13B p.Ser247= (c.741C>T) is associated with Cohen syndrome (ClinVar).

How common is VPS13B p.Ser247= (c.741C>T) in the general population?

VPS13B p.Ser247= (c.741C>T) is absent from gnomAD v4.1 (gnomAD).

VPS13B p.Ser247=

c.741C>T · VCV3632099

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 0.85	GERP 2.3, phastCons 1
Overall
CADD	11.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VPS13B
Protein: p.Ser247=
Coding: c.741C>T
MANE Select: NM_152564
Type: single nucleotide variant
Location: chr8:99111258 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Residue 247: 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)

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 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
VPS13B c.2516-2A>G 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-ser247 (accessed [today's date]).

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