Is VCL p.Ile388= (c.1164C>T) pathogenic?

VCL p.Ile388= (c.1164C>T) is classified Benign/Likely benign in VCL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-26). Rare (popmax 0.123%, sas); Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Ile388= (c.1164C>T)?

VCL p.Ile388= (c.1164C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.Ile388= (c.1164C>T) in the general population?

VCL p.Ile388= (c.1164C>T) is rare (popmax 0.123%, sas) (gnomAD).

VCL p.Ile388=

c.1164C>T · rs370852950 · VCV706653

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.123%, sas)

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 -15	GERP -5.6
Overall
CADD	1.542	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% South Asian · 112/91,076 alleles

Filtering AF 0.104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0975%

Overall 0.01% 162/1,613,800 alleles · rare exomes 153/1,461,754 · genomes 9/152,046 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.123%	813
Finnishnot grpmax-eligible	0.0219%	4,565
East Asian	0.00446%	22,444
Admixed American	0.00333%	29,986
European (non-Finnish)	0.00254%	39,334
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00134%	74,866

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.Ile388=
Coding: c.1164C>T
MANE Select: NM_014000
dbSNP: rs370852950
Type: single nucleotide variant
Location: chr10:74089337 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 388: 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

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-ile388 (accessed [today's date]).

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