Is VCL p.His27= (c.81C>T) pathogenic?

VCL p.His27= (c.81C>T) is classified Conflicting classifications of pathogenicity in VCL (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0541%, amr); Associated with Cardiovascular phenotype.

What condition is associated with VCL p.His27= (c.81C>T)?

VCL p.His27= (c.81C>T) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1W (ClinVar).

How common is VCL p.His27= (c.81C>T) in the general population?

VCL p.His27= (c.81C>T) is ultra-rare (popmax 0.0541%, amr) (gnomAD).

VCL p.His27=

c.81C>T · rs200733607 · VCV202145

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0541%, amr)

Conditions

Cardiovascular phenotype

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.3	GERP 0.52, phastCons 1
Overall
CADD	13.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0541% Admixed American · 32/59,154 alleles

Filtering AF 0.0393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0343%

Overall 0.0313% 502/1,604,596 alleles · ultra-rare exomes 476/1,452,258 · genomes 26/152,338 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0541%	1,849
European (non-Finnish)	0.0379%	2,641
Remaining individualsnot grpmax-eligible	0.0226%	4,430
African / African-American	0.012%	8,307
Finnishnot grpmax-eligible	0.00317%	31,520

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.His27=
Coding: c.81C>T
MANE Select: NM_014000
dbSNP: rs200733607
Type: single nucleotide variant
Location: chr10:73998288 (GRCh38)

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

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-his27 (accessed [today's date]).

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