Is VCL p.Asp557= (c.1671C>T) pathogenic?

VCL p.Asp557= (c.1671C>T) is classified Benign/Likely benign in VCL (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.79%, sas); Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Asp557= (c.1671C>T)?

VCL p.Asp557= (c.1671C>T) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.Asp557= (c.1671C>T) in the general population?

VCL p.Asp557= (c.1671C>T) is low-frequency (popmax 1.79%, sas) (gnomAD).

VCL p.Asp557=

c.1671C>T · rs137877092 · VCV45587

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.79%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.56	GERP 1.7, phastCons 1
Overall
CADD	8.611	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.79% South Asian · 1,631/91,088 alleles

Filtering AF 1.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.69%

Overall 0.292% 4,721/1,614,146 alleles · low-frequency exomes 4,319/1,461,870 · genomes 402/152,276 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.79%	56
Finnishnot grpmax-eligible	1.62%	62
Middle Eastern	0.809%	124
Ashkenazi Jewishnot grpmax-eligible	0.473%	211
Remaining individualsnot grpmax-eligible	0.381%	263
European (non-Finnish)	0.132%	760
Admixed American	0.09%	1,111
African / African-American	0.0227%	4,414
East Asian	0.00446%	22,439

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.Asp557=
Coding: c.1671C>T
MANE Select: NM_014000
dbSNP: rs137877092
Type: single nucleotide variant
Location: chr10:74095783 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 557: 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: cardiomyopathy 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-asp557 (accessed [today's date]).

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