Is VCL p.Pro486fs (c.1457del) pathogenic?

VCL p.Pro486fs (c.1457del) is classified Uncertain significance in VCL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-27). Absent from gnomAD; Associated with dilated cardiomyopathy 1W.

What condition is associated with VCL p.Pro486fs (c.1457del)?

VCL p.Pro486fs (c.1457del) is associated with dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.Pro486fs (c.1457del) in the general population?

VCL p.Pro486fs (c.1457del) is absent from gnomAD (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

VCL p.Pro486fs

c.1457del · rs2549225360 · VCV2078743

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

dilated cardiomyopathy 1W

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 11 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.97	GERP -3.4, phastCons 0.99

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: VCL
Protein: p.Pro486fs
Coding: c.1457del
MANE Select: NM_014000
dbSNP: rs2549225360
Type: Deletion
Location: chr10:74094374 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 486: the 'n-terminal globular head' region; the '3 x 112 aa tandem repeats' region; an α-helix

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

Disease context

dilated cardiomyopathy 1W — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

VCL p.Pro486Leu Uncertain significance ★★ ⚠ same residue
VCL p.Pro486= Likely benign ★★ same residue
VCL c.168+1del Uncertain significance ★★ same condition
VCL p.Asp944fs Uncertain significance ★★ same condition
VCL p.Gln334_Leu338del Uncertain significance ★★ same condition
VCL p.Glu200fs Uncertain significance ★★ same condition
VCL p.Gly926_Val927del Uncertain significance ★★ same condition
VCL p.Pro796fs Uncertain significance ★★ 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-pro486fs (accessed [today's date]).

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