Is VCL p.Val514= (c.1542C>T) pathogenic?

VCL p.Val514= (c.1542C>T) is classified Benign/Likely benign in VCL (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-05-01). Low-frequency (popmax 1.21%, afr); Associated with cardiomyopathy.

What condition is associated with VCL p.Val514= (c.1542C>T)?

VCL p.Val514= (c.1542C>T) is associated with cardiomyopathy, dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.Val514= (c.1542C>T) in the general population?

VCL p.Val514= (c.1542C>T) is low-frequency (popmax 1.21%, afr) (gnomAD).

VCL p.Val514=

c.1542C>T · rs7904077 · VCV45581

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.21%, afr)

Conditions

cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.9	GERP -5.4
Overall
CADD	0.053	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.21% African / African-American · 907/75,018 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.12%

Overall 0.0625% 1,008/1,613,324 alleles · low-frequency exomes 469/1,461,058 · genomes 539/152,266 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.21%	83
Admixed American	0.0752%	1,331
Remaining individualsnot grpmax-eligible	0.072%	1,389
Middle Eastern	0.0495%	2,021
East Asian	0.00223%	44,866
European (non-Finnish)	0.000593%	168,527

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.Val514=
Coding: c.1542C>T
MANE Select: NM_014000
dbSNP: rs7904077
Type: single nucleotide variant
Location: chr10:74094460 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 514: 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

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

Also linked: dilated cardiomyopathy 1W

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-val514 (accessed [today's date]).

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