Is VCL p.Pro860fs (c.2579del) pathogenic?

VCL p.Pro860fs (c.2579del) is classified Uncertain significance in VCL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-11). Very rare (popmax 0.00136%, nfe); Associated with dilated cardiomyopathy 1W.

What condition is associated with VCL p.Pro860fs (c.2579del)?

VCL p.Pro860fs (c.2579del) is associated with dilated cardiomyopathy 1W, hypertrophic cardiomyopathy 15 (ClinVar).

How common is VCL p.Pro860fs (c.2579del) in the general population?

VCL p.Pro860fs (c.2579del) is very rare (popmax 0.00136%, nfe) (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.Pro860fs

c.2579del · rs1840179829 · VCV968156

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

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 18 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,180,018 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.000991% 16/1,614,120 alleles · very rare exomes 16/1,461,890 · genomes 0/152,230 · 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: VCL
Protein: p.Pro860fs
Coding: c.2579del
MANE Select: NM_014000
dbSNP: rs1840179829
Type: Deletion
Location: chr10:74108989 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 860: the 'linker (pro-rich)' region; the 'disordered' 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

Also linked: hypertrophic cardiomyopathy 15

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 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
VCL c.169-11del Benign/Likely benign ★★ same condition
VCL c.2023-34_2023-4del 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-pro860fs (accessed [today's date]).

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