Is VCL p.Ala933= (c.2799G>A) pathogenic?

VCL p.Ala933= (c.2799G>A) is classified Benign/Likely benign in VCL (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-25). Ultra-rare (popmax 0.0106%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Ala933= (c.2799G>A)?

VCL p.Ala933= (c.2799G>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.Ala933= (c.2799G>A) in the general population?

VCL p.Ala933= (c.2799G>A) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

VCL p.Ala933=

c.2799G>A · rs199507346 · VCV137900

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, 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 3	GERP 0.58, phastCons 1
Overall
CADD	11.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0106% European (non-Finnish) · 125/1,180,022 alleles

Filtering AF 0.00906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00844%

Overall 0.00812% 131/1,614,126 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0106%	9,440
Remaining individualsnot grpmax-eligible	0.0048%	20,837
East Asian	0.00223%	44,874
Admixed American	0.00167%	60,020
African / African-American	0.00133%	75,018

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.Ala933=
Coding: c.2799G>A
MANE Select: NM_014000
dbSNP: rs199507346
Type: single nucleotide variant
Location: chr10:74111962 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 933: the 'c-terminal tail' region

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 p.Ala933Glu Uncertain significance ★ ⚠ same residue
VCL p.Ala933Val Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ala933 (accessed [today's date]).

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