Is CAV3 p.Ala11Val (c.32C>T) pathogenic?

CAV3 p.Ala11Val (c.32C>T) is classified Conflicting classifications of pathogenicity in CAV3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-22). AlphaMissense: likely benign (0.0962); Very rare (popmax 0.0011%, sas); Associated with Cardiovascular phenotype.

What condition is associated with CAV3 p.Ala11Val (c.32C>T)?

CAV3 p.Ala11Val (c.32C>T) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is CAV3 p.Ala11Val (c.32C>T) in the general population?

CAV3 p.Ala11Val (c.32C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CAV3 p.Ala11Val (c.32C>T)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

CAV3 p.Ala11Val

c.32C>T · rs867194464 · VCV519540

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.406	indeterminate
SaProt	LLR -7.44	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 12 kb · p 0.021 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,010 alleles

Overall 0.000658% 1/152,074 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.Ala11Val
Coding: c.32C>T
MANE Select: NM_033337
dbSNP: rs867194464
Type: single nucleotide variant
Location: chr3:8733908 (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

Similar variants

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 p.Ala102Val Uncertain significance ★★ ⚠ same condition
CAV3 p.Ala134Glu Uncertain significance ★★ ⚠ same condition
CAV3 p.Ala134Pro 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-ala11val (accessed [today's date]).

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