Is VCL p.Pro507= (c.1521C>T) pathogenic?

VCL p.Pro507= (c.1521C>T) is classified Conflicting classifications of pathogenicity in VCL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2020-10-21). Very rare (popmax 0.00136%, nfe); Associated with cardiomyopathy.

What condition is associated with VCL p.Pro507= (c.1521C>T)?

VCL p.Pro507= (c.1521C>T) is associated with cardiomyopathy (ClinVar).

How common is VCL p.Pro507= (c.1521C>T) in the general population?

VCL p.Pro507= (c.1521C>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

VCL p.Pro507=

c.1521C>T · rs1564529609 · VCV626456

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Conditions

cardiomyopathy

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 0.003	GERP -3, phastCons 0.83
Overall
CADD	8.732	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,179,968 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.000991% 16/1,614,042 alleles · very rare exomes 16/1,461,756 · genomes 0/152,286 · joint denominator

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.Pro507=
Coding: c.1521C>T
MANE Select: NM_014000
dbSNP: rs1564529609
Type: single nucleotide variant
Location: chr10:74094439 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 507: the 'n-terminal globular head' region; the '3 x 112 aa tandem repeats' region

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

Similar variants

VCL p.Pro507Ser Uncertain significance ★ ⚠ same residue
VCL p.Ala340Val Uncertain significance ★★ ⚠ same condition
VCL p.Ala630Thr Uncertain significance ★★ ⚠ same condition
VCL p.Ala803Thr Uncertain significance ★★ ⚠ same condition
VCL p.Arg105Ter Uncertain significance ★★ same condition
VCL p.Arg762Trp Uncertain significance ★★ ⚠ same condition
VCL p.Arg823Trp Uncertain significance ★★ ⚠ same condition
VCL p.Glu1089Asp 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-pro507 (accessed [today's date]).

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