Is VCL p.Asp256= (c.768T>C) pathogenic?

VCL p.Asp256= (c.768T>C) is classified Benign/Likely benign in VCL (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-02-04). Common (popmax 21.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Asp256= (c.768T>C)?

VCL p.Asp256= (c.768T>C) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1W (ClinVar).

VCL p.Asp256=

Q: How common is VCL p.Asp256= (c.768T>C) in the general population?

VCL p.Asp256= (c.768T>C) is common (popmax 21.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.768T>C · rs56413529 · VCV36898

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Common

common (popmax 21.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

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 0.33	GERP -4, phastCons 1
Overall
CADD	8.072	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.6% African / African-American · 16,226/74,956 alleles

Filtering AF 21.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.3%

Overall 1.19% 19,200/1,614,064 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	21.6%	5
Ashkenazi Jewishnot grpmax-eligible	1.63%	61
Remaining individualsnot grpmax-eligible	1.59%	63
Middle Eastern	1.42%	70
Admixed American	1.37%	73
South Asian	0.0659%	1,518
European (non-Finnish)	0.045%	2,222
East Asian	0.00446%	22,438

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.Asp256=
Coding: c.768T>C
MANE Select: NM_014000
dbSNP: rs56413529
Type: single nucleotide variant
Location: chr10:74074888 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 256: the 'n-terminal globular head' region

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 hypertrophic cardiomyopathy 15

Similar variants

VCL p.Asp256Glu Uncertain significance ★★ ⚠ same residue
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

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-asp256 (accessed [today's date]).

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