Is VCL p.Val739= (c.2217A>T) pathogenic?

VCL p.Val739= (c.2217A>T) is classified Likely benign in VCL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Val739= (c.2217A>T)?

VCL p.Val739= (c.2217A>T) is associated with Cardiovascular phenotype (ClinVar).

How common is VCL p.Val739= (c.2217A>T) in the general population?

VCL p.Val739= (c.2217A>T) is absent from gnomAD v4.1 (gnomAD).

VCL p.Val739=

c.2217A>T · VCV3467829

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	donor loss, 3 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.22	GERP -5.8, phastCons 0.45
Overall
CADD	4.365	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VCL
Protein: p.Val739=
Coding: c.2217A>T
MANE Select: NM_014000
Type: single nucleotide variant
Location: chr10:74105136 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 739: 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

Similar variants

VCL c.1352+5G>A Uncertain significance ★★ same condition
VCL c.1543+4A>G Uncertain significance ★★ same condition
VCL c.2132-3C>A Uncertain significance ★★ same condition
VCL c.239+3G>A Uncertain significance ★★ same condition
VCL p.Ala1023Thr Uncertain significance ★★ ⚠ same condition
VCL p.Ala1120Thr Uncertain significance ★★ ⚠ same condition
VCL p.Ala257Thr Uncertain significance ★★ ⚠ same condition
VCL p.Ala340Val 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-val739 (accessed [today's date]).

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