Is VCL p.Val675= (c.2025G>A) pathogenic?

VCL p.Val675= (c.2025G>A) is classified Conflicting classifications of pathogenicity in VCL (ClinVar, Conflicting submitters, 20 submitters; last evaluated 2026-02-04). Rare (popmax 0.547%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Val675= (c.2025G>A)?

VCL p.Val675= (c.2025G>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.Val675= (c.2025G>A) in the general population?

VCL p.Val675= (c.2025G>A) is rare (popmax 0.547%, nfe) (gnomAD).

VCL p.Val675=

c.2025G>A · rs140766884 · VCV36896

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 20 submitters

gnomAD v4.1

Rare

rare (popmax 0.547%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.58	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -6.1	GERP -5.8
Overall
CADD	7.598	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.547% European (non-Finnish) · 6,450/1,179,852 alleles

Filtering AF 0.535% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.531%

Overall 0.43% 6,934/1,613,958 alleles · rare exomes 6,556/1,461,666 · genomes 378/152,292 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.547%	183
Remaining individualsnot grpmax-eligible	0.421%	238
Finnishnot grpmax-eligible	0.141%	711
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0786%	1,272
Admixed American	0.0766%	1,305
South Asian	0.0242%	4,140
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802

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.Val675=
Coding: c.2025G>A
MANE Select: NM_014000
dbSNP: rs140766884
Type: single nucleotide variant
Location: chr10:74103822 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 675: 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

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

Also linked: cardiomyopathy 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-val675 (accessed [today's date]).

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