Is VCL p.Ile12= (c.36C>T) pathogenic?

VCL p.Ile12= (c.36C>T) is classified Conflicting classifications of pathogenicity in VCL (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-11). Very rare (popmax 0.0022%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Ile12= (c.36C>T)?

VCL p.Ile12= (c.36C>T) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.Ile12= (c.36C>T) in the general population?

VCL p.Ile12= (c.36C>T) is very rare (popmax 0.0022%, nfe) (gnomAD).

VCL p.Ile12=

c.36C>T · rs774195260 · VCV879269

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

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 0.025	GERP -3.4, phastCons 0.79
Overall
CADD	11.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% European (non-Finnish) · 26/1,179,540 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00167% 27/1,612,796 alleles · very rare exomes 26/1,460,540 · genomes 1/152,256 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,367
South Asian	0.0011%	90,864

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.Ile12=
Coding: c.36C>T
MANE Select: NM_014000
dbSNP: rs774195260
Type: single nucleotide variant
Location: chr10:73998243 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 12: 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-ile12 (accessed [today's date]).

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