Is VCL p.Arg113= (c.339G>A) pathogenic?

VCL p.Arg113= (c.339G>A) is classified Benign/Likely benign in VCL (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 21.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Arg113= (c.339G>A)?

VCL p.Arg113= (c.339G>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1W (ClinVar).

VCL p.Arg113=

Q: How common is VCL p.Arg113= (c.339G>A) in the general population?

VCL p.Arg113= (c.339G>A) is common (popmax 21.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.339G>A · rs56314318 · VCV36897

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 21.5%, 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 1.2	GERP -2.5, phastCons 1
Overall
CADD	7.414	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.5% African / African-American · 16,146/74,928 alleles

Filtering AF 21.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.2%

Overall 1.18% 19,043/1,613,974 alleles · common exomes 9,521/1,461,846 · genomes 9,522/152,128 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	21.5%	5
Ashkenazi Jewishnot grpmax-eligible	1.63%	61
Remaining individualsnot grpmax-eligible	1.52%	66
Middle Eastern	1.41%	71
Admixed American	1.36%	74
South Asian	0.0725%	1,380
European (non-Finnish)	0.0421%	2,374

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.Arg113=
Coding: c.339G>A
MANE Select: NM_014000
dbSNP: rs56314318
Type: single nucleotide variant
Location: chr10:74070769 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 113: 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 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-arg113 (accessed [today's date]).

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