Is VCL p.Ala1111Phe (c.3331_3332delinsTT) pathogenic?

VCL p.Ala1111Phe (c.33313332delinsTT) is classified Uncertain significance in VCL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-08). Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Ala1111Phe (c.3331_3332delinsTT)?

VCL p.Ala1111Phe (c.3331_3332delinsTT) is associated with Cardiovascular phenotype (ClinVar).

VCL p.Ala1111Phe

c.3331_3332delinsTT · VCV3979536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 6,073 bp · p 2.6e-15 · regional, not allelic

Variant & gene context

Gene: VCL
Protein: p.Ala1111Phe
Coding: c.3331_3332delinsTT
MANE Select: NM_014000
Type: Indel
Location: chr10:74118095 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 1111: the 'c-terminal tail' 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 p.Ala1111= Benign/Likely benign ★★ same residue
VCL p.Ala1111Ser Uncertain significance ★ same residue
VCL p.Ala1111Val Uncertain significance ★ ⚠ same residue
VCL p.Pro942_Pro943delinsLeuAla Uncertain significance ★ same condition
VCL p.Pro942Ser Conflicting classifications of pathogenicity ★ same condition
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

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-ala1111phe (accessed [today's date]).

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