Is CAV3 p.Glu4fs (c.10_17del) pathogenic?

CAV3 p.Glu4fs (c.1017del) is classified Conflicting classifications of pathogenicity in CAV3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-30). Very rare (popmax 0.00937%, afr); Associated with long QT syndrome.

What condition is associated with CAV3 p.Glu4fs (c.10_17del)?

CAV3 p.Glu4fs (c.10_17del) is associated with long QT syndrome (ClinVar).

How common is CAV3 p.Glu4fs (c.10_17del) in the general population?

CAV3 p.Glu4fs (c.10_17del) is very rare (popmax 0.00937%, afr) (gnomAD).

CAV3 p.Glu4fs

c.10_17del · rs778914298 · VCV290919

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00937%, afr)

Conditions

long QT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 2
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00937% African / African-American · 7/74,722 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000499% 8/1,601,890 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00937%	10,675
Remaining individualsnot grpmax-eligible	0.00161%	62,088

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.Glu4fs
Coding: c.10_17del
MANE Select: NM_033337
dbSNP: rs778914298
Type: Deletion
Location: chr3:8733883 (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

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAV3 p.Glu4Gly Uncertain significance ★ ⚠ same residue
CAV3 p.Asp55fs Uncertain significance ★★ same condition
CAV3 p.Cys106fs Uncertain significance ★★ same condition
CAV3 p.Ter152LysextTer? Uncertain significance ★★ same condition
CAV3 p.Leu86fs Pathogenic ★ same condition
CAV3 p.Leu24_Asp28del Uncertain significance ★ same condition
CAV3 p.Met2fs Conflicting classifications of pathogenicity ★ same condition
CAV3 c.114+2T>C Pathogenic ★★ 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-glu4fs (accessed [today's date]).

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