Is CAV3 p.Lys30Arg (c.89A>G) pathogenic?

CAV3 p.Lys30Arg (c.89A>G) is classified Uncertain significance in CAV3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-03-10). AlphaMissense: likely benign (0.0735); Ultra-rare (popmax 0.0167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with CAV3 p.Lys30Arg (c.89A>G)?

CAV3 p.Lys30Arg (c.89A>G) is associated with Cardiovascular phenotype, long QT syndrome, long QT syndrome 9 (ClinVar).

How common is CAV3 p.Lys30Arg (c.89A>G) in the general population?

CAV3 p.Lys30Arg (c.89A>G) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about CAV3 p.Lys30Arg (c.89A>G)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

CAV3 p.Lys30Arg

c.89A>G · rs753431407 · VCV637987

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.406	indeterminate
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 12 kb · p 0.021 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0167% Admixed American · 10/59,976 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.00149% 24/1,610,534 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,998
Remaining individualsnot grpmax-eligible	0.00802%	12,471
African / African-American	0.00134%	74,730
South Asian	0.0011%	90,968
European (non-Finnish)	0.000595%	168,148

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.Lys30Arg
Coding: c.89A>G
MANE Select: NM_033337
dbSNP: rs753431407
Type: single nucleotide variant
Location: chr3:8733965 (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 long QT syndrome 9

Similar variants

CAV3 p.Lys30Ter Uncertain significance ★★ same residue
CAV3 p.Lys30Gln 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-lys30arg (accessed [today's date]).

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