Is CAV3 p.Leu79Arg (c.236T>G) pathogenic?

CAV3 p.Leu79Arg (c.236T>G) is classified Uncertain significance in CAV3 (ClinVar, Single submitter, 3 submitters; last evaluated 2019-11-08). AlphaMissense: likely pathogenic (0.9306); Very rare (popmax 0.004%, afr); Associated with long QT syndrome.

What condition is associated with CAV3 p.Leu79Arg (c.236T>G)?

CAV3 p.Leu79Arg (c.236T>G) is associated with long QT syndrome, long QT syndrome 9 (ClinVar).

How common is CAV3 p.Leu79Arg (c.236T>G) in the general population?

CAV3 p.Leu79Arg (c.236T>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CAV3 p.Leu79Arg (c.236T>G)?

AlphaMissense predicts likely pathogenic (score 0.9306) — an in-silico prediction, not a clinical call.

CAV3 p.Leu79Arg

c.236T>G · rs121909282 · VCV8296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9306 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.9306	likely pathogenic
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -13.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 12 kb · p 0.021 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,944 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,042 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.Leu79Arg
Coding: c.236T>G
MANE Select: NM_033337
dbSNP: rs121909282
Type: single nucleotide variant
Location: chr3:8745647 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 88.54
Residue 79: a UniProt-annotated variant site (in lqt9 and sids); the 'required for interaction with dag1' region

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

Also linked: long QT syndrome 9

Similar variants

CAV3 p.Leu79= Likely benign ★ 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
CAV3 c.*592G>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-leu79arg (accessed [today's date]).

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