Is VCL p.Ala524= (c.1572C>T) pathogenic?

VCL p.Ala524= (c.1572C>T) is classified Benign/Likely benign in VCL (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-01-25). Rare (popmax 0.24%, afr); Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Ala524= (c.1572C>T)?

VCL p.Ala524= (c.1572C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1W, hypertrophic cardiomyopathy 15 (ClinVar).

How common is VCL p.Ala524= (c.1572C>T) in the general population?

VCL p.Ala524= (c.1572C>T) is rare (popmax 0.24%, afr) (gnomAD).

VCL p.Ala524=

c.1572C>T · rs138566234 · VCV45584

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

rare (popmax 0.24%, afr)

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 -14	GERP -5.2
Overall
CADD	6.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.24% African / African-American · 180/75,016 alleles

Filtering AF 0.211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.2%

Overall 0.0187% 302/1,614,012 alleles · rare exomes 185/1,461,782 · genomes 117/152,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.24%	417
Admixed American	0.0317%	3,159
Remaining individualsnot grpmax-eligible	0.0304%	3,289
Middle Eastern	0.0167%	5,978
European (non-Finnish)	0.00695%	14,390
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Ala524=
Coding: c.1572C>T
MANE Select: NM_014000
dbSNP: rs138566234
Type: single nucleotide variant
Location: chr10:74095684 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 524: 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

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

Also linked: dilated cardiomyopathy 1W hypertrophic cardiomyopathy 15

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-ala524 (accessed [today's date]).

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