Is VCL p.Ser809= (c.2427C>T) pathogenic?

VCL p.Ser809= (c.2427C>T) is classified Conflicting classifications of pathogenicity in VCL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0507%, afr); Associated with dilated cardiomyopathy 1W.

What condition is associated with VCL p.Ser809= (c.2427C>T)?

VCL p.Ser809= (c.2427C>T) is associated with dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.Ser809= (c.2427C>T) in the general population?

VCL p.Ser809= (c.2427C>T) is ultra-rare (popmax 0.0507%, afr) (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.Ser809=

c.2427C>T · rs183739128 · VCV300794

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, afr)

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 -0.12	GERP -3.3, phastCons 0.78
Overall
CADD	7.775	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0507% African / African-American · 38/74,960 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0334%

Overall 0.00354% 57/1,612,200 alleles · ultra-rare exomes 29/1,459,920 · genomes 28/152,280 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0507%	1,973
Admixed American	0.00667%	15,004
South Asian	0.0033%	30,327
Remaining individualsnot grpmax-eligible	0.0016%	62,326
European (non-Finnish)	0.000932%	107,269

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.Ser809=
Coding: c.2427C>T
MANE Select: NM_014000
dbSNP: rs183739128
Type: single nucleotide variant
Location: chr10:74105346 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 809: a modified residue (phosphoserine); the 'n-terminal globular head' region

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-ser809 (accessed [today's date]).

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