Is CAV3 p.Val139= (c.417C>T) pathogenic?

CAV3 p.Val139= (c.417C>T) is classified Conflicting classifications of pathogenicity in CAV3 (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-01-28). Rare (popmax 0.115%, mid); Associated with Cardiovascular phenotype.

What condition is associated with CAV3 p.Val139= (c.417C>T)?

CAV3 p.Val139= (c.417C>T) is associated with Cardiovascular phenotype, long QT syndrome, cardiomyopathy (ClinVar).

How common is CAV3 p.Val139= (c.417C>T) in the general population?

CAV3 p.Val139= (c.417C>T) is rare (popmax 0.115%, mid) (gnomAD).

CAV3 p.Val139=

c.417C>T · rs147250678 · VCV35804

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.36	GERP -5.9, phastCons 0.038
Overall
CADD	3.724	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.0388% 626/1,613,698 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.358%	279
Middle Easterngrpmax	0.115%	866
Remaining individualsnot grpmax-eligible	0.04%	2,500
European (non-Finnish)	0.0388%	2,576
Admixed American	0.02%	5,002
Finnishnot grpmax-eligible	0.0157%	6,354
African / African-American	0.00799%	12,511
South Asian	0.0022%	45,536

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CAV3
Protein: p.Val139=
Coding: c.417C>T
MANE Select: NM_033337
dbSNP: rs147250678
Type: single nucleotide variant
Location: chr3:8745828 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 88.54

Full CAV3 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: long QT syndrome cardiomyopathy caveolinopathy

Similar variants

CAV3 p.Val139Ala Uncertain significance ★★ ⚠ same residue
CAV3 p.Val139Ile Uncertain significance ★ ⚠ same residue
CAV3 c.114+2T>C Pathogenic ★★ same condition
CAV3 p.Ala46Thr Pathogenic/Likely pathogenic ★★ same condition
CAV3 p.Arg27Gln Pathogenic ★★ same condition
CAV3 p.Trp71Ter Pathogenic/Likely pathogenic ★★ same condition
CAV3 c.114+5G>C Uncertain significance ★★ same condition
CAV3 c.*134G>A 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/cav3-p-val139 (accessed [today's date]).

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