Is CAV3 p.Arg27Ter (c.79C>T) pathogenic?

CAV3 p.Arg27Ter (c.79C>T) is classified Pathogenic in CAV3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). Very rare (popmax 0.00134%, afr); Associated with long QT syndrome.

What condition is associated with CAV3 p.Arg27Ter (c.79C>T)?

CAV3 p.Arg27Ter (c.79C>T) is associated with long QT syndrome (ClinVar).

How common is CAV3 p.Arg27Ter (c.79C>T) in the general population?

CAV3 p.Arg27Ter (c.79C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

CAV3 p.Arg27Ter

c.79C>T · rs199476324 · VCV846689

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

long QT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (1 of 2, 35 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.67, phastCons 1
Overall
CADD	41.0	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 0.00134% African / African-American · 1/74,784 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000548% 8/1,460,146 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,784
South Asian	0.0011%	90,978
European (non-Finnish)	0.000509%	196,415

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.Arg27Ter
Coding: c.79C>T
MANE Select: NM_033337
dbSNP: rs199476324
Type: single nucleotide variant
Location: chr3:8733955 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 88.54
Residue 27: a UniProt-annotated variant site (in hypck, rmd2 and mpdt)

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.Arg27Gln Pathogenic ★★ same residue
CAV3 p.Arg27Gly Pathogenic ★ same residue
CAV3 p.Arg27Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
CAV3 c.114+2T>C Pathogenic ★★ same condition
CAV3 p.Ala46Thr Pathogenic/Likely pathogenic ★★ same condition
CAV3 p.Trp71Ter Pathogenic/Likely pathogenic ★★ same condition
CAV3 c.114+5G>C Uncertain significance ★★ same condition
CAV3 p.Ala102Val 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-arg27ter (accessed [today's date]).

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