Is CAV3 p.Met2fs (c.6_7del) pathogenic?

CAV3 p.Met2fs (c.67del) is classified Conflicting classifications of pathogenicity in CAV3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-09-06). Very rare (popmax 0.000171%, nfe); Associated with long QT syndrome.

What condition is associated with CAV3 p.Met2fs (c.6_7del)?

CAV3 p.Met2fs (c.6_7del) is associated with long QT syndrome (ClinVar).

How common is CAV3 p.Met2fs (c.6_7del) in the general population?

CAV3 p.Met2fs (c.6_7del) is very rare (popmax 0.000171%, nfe) (gnomAD).

CAV3 p.Met2fs

c.6_7del · rs1060502318 · VCV409261

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

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 7.8	GERP 2.1, phastCons 1
Overall
CADD	32.0	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 0.000171% European (non-Finnish) · 2/1,170,644 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,603,634 alleles · very rare

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.Met2fs
Coding: c.6_7del
MANE Select: NM_033337
dbSNP: rs1060502318
Type: Deletion
Location: chr3:8733882 (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.Met2Thr 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.Glu4fs Conflicting classifications of pathogenicity ★ same condition
CAV3 p.Leu24_Asp28del Uncertain significance ★ 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-met2fs (accessed [today's date]).

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