Is VCL p.Val1127= (c.3381T>C) pathogenic?

VCL p.Val1127= (c.3381T>C) is classified Likely benign in VCL (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-20). Very rare (popmax 0.00446%, eas); Associated with Cardiovascular phenotype.

What condition is associated with VCL p.Val1127= (c.3381T>C)?

VCL p.Val1127= (c.3381T>C) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1W, hypertrophic cardiomyopathy 15 (ClinVar).

How common is VCL p.Val1127= (c.3381T>C) in the general population?

VCL p.Val1127= (c.3381T>C) is very rare (popmax 0.00446%, eas) (gnomAD).

VCL p.Val1127=

c.3381T>C · rs943734765 · VCV378850

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.021	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1, phastCons 1
Overall
CADD	5.895	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00031% 5/1,613,978 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,442
African / African-American	0.00267%	37,438
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Val1127=
Coding: c.3381T>C
MANE Select: NM_014000
dbSNP: rs943734765
Type: single nucleotide variant
Location: chr10:74118145 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.69 · 37 PDB
Residue 1127: the 'c-terminal tail' region; the 'facilitates phospholipid membrane insertion' 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: dilated cardiomyopathy 1W hypertrophic cardiomyopathy 15

Similar variants

VCL p.Val1127Ala Uncertain significance ★ ⚠ same residue
VCL p.Val1127Ile Uncertain significance ★ ⚠ 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-val1127 (accessed [today's date]).

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