Is VCL p.Leu722= (c.2164C>T) pathogenic?

VCL p.Leu722= (c.2164C>T) is classified Likely benign in VCL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). Very rare (popmax 0.0011%, sas); Associated with dilated cardiomyopathy 1W.

What condition is associated with VCL p.Leu722= (c.2164C>T)?

VCL p.Leu722= (c.2164C>T) is associated with dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.Leu722= (c.2164C>T) in the general population?

VCL p.Leu722= (c.2164C>T) is very rare (popmax 0.0011%, sas) (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.Leu722=

c.2164C>T · rs2131928315 · VCV1662504

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

dilated cardiomyopathy 1W

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 2.3	GERP 2, phastCons 1
Overall
CADD	8.757	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Overall 0.000137% 2/1,461,886 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	8.47e-05%	1,180,034

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.Leu722=
Coding: c.2164C>T
MANE Select: NM_014000
dbSNP: rs2131928315
Type: single nucleotide variant
Location: chr10:74105083 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 722: 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

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 c.1176+4G>C Uncertain significance ★★ same condition
VCL c.1352+5G>A Uncertain significance ★★ same condition
VCL c.1543+1G>T Uncertain significance ★★ same condition
VCL c.1543+4A>G Uncertain significance ★★ same condition
VCL c.1743+6A>G Uncertain significance ★★ same condition
VCL c.1744-1G>T Uncertain significance ★★ same condition
VCL c.2022+5G>T Uncertain significance ★★ same condition
VCL c.2023-1G>C 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-leu722 (accessed [today's date]).

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