Is VCL p.Ile245fs (c.733_736del) pathogenic?

VCL p.Ile245fs (c.733736del) is classified Uncertain significance in VCL (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-02). Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Ile245fs (c.733_736del)?

VCL p.Ile245fs (c.733_736del) is associated with Cardiovascular phenotype (ClinVar).

VCL p.Ile245fs

c.733_736del · VCV4824340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.28	GERP -0.53, phastCons 0.98

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

Variant & gene context

Gene: VCL
Protein: p.Ile245fs
Coding: c.733_736del
MANE Select: NM_014000
Type: Deletion
Location: chr10:74074853 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 245: the 'n-terminal globular head' region; an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VCL p.Asp944fs Uncertain significance ★★ same condition
VCL p.Gln334_Leu338del Uncertain significance ★★ same condition
VCL p.Glu200fs Uncertain significance ★★ same condition
VCL c.2023-1177_2051del Uncertain significance ★ same condition
VCL p.Arg680fs Uncertain significance ★ same condition
VCL p.Leu421fs Uncertain significance ★ same condition
VCL p.Leu955del Conflicting classifications of pathogenicity ★ same condition
VCL p.Pro943fs Conflicting classifications of pathogenicity ★ ⚠ 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/vcl-p-ile245fs (accessed [today's date]).

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