Is VCL p.Val55Phe (c.163G>T) pathogenic?

VCL p.Val55Phe (c.163G>T) is classified Uncertain significance in VCL (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-11-07). AlphaMissense: likely pathogenic (0.9378); Very rare (popmax 0.000703%, nfe); Associated with familial dilated cardiomyopathy.

What condition is associated with VCL p.Val55Phe (c.163G>T)?

VCL p.Val55Phe (c.163G>T) is associated with familial dilated cardiomyopathy, cardiomyopathy, dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.Val55Phe (c.163G>T) in the general population?

VCL p.Val55Phe (c.163G>T) is very rare (popmax 0.000703%, nfe) (gnomAD).

What do computational predictors say about VCL p.Val55Phe (c.163G>T)?

AlphaMissense predicts likely pathogenic (score 0.9378) — an in-silico prediction, not a clinical call.

VCL p.Val55Phe

c.163G>T · rs755441334 · VCV229631

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9378 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000703%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.9378	likely pathogenic
REVEL	0.608	indeterminate
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 73 kb · p 0.00039 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000703% European (non-Finnish) · 8/1,138,216 alleles

Filtering AF 0.000302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000219%

Overall 0.000521% 8/1,534,466 alleles · very rare exomes 5/1,382,354 · genomes 3/152,112 · joint denominator

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.Val55Phe
Coding: c.163G>T
MANE Select: NM_014000
dbSNP: rs755441334
Type: single nucleotide variant
Location: chr10:73998370 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 55: 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

familial dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy dilated cardiomyopathy 1W

Similar variants

VCL p.Val55Leu Uncertain significance ★ ⚠ same residue
VCL p.Val55= Likely benign ★ 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-val55phe (accessed [today's date]).

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