Is CAV3 p.Pro29His (c.86C>A) pathogenic?

CAV3 p.Pro29His (c.86C>A) is classified Uncertain significance in CAV3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-13). AlphaMissense: likely pathogenic (0.8919); Very rare (popmax 0.00017%, nfe); Associated with long QT syndrome.

What condition is associated with CAV3 p.Pro29His (c.86C>A)?

CAV3 p.Pro29His (c.86C>A) is associated with long QT syndrome (ClinVar).

How common is CAV3 p.Pro29His (c.86C>A) in the general population?

CAV3 p.Pro29His (c.86C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CAV3 p.Pro29His (c.86C>A)?

AlphaMissense predicts likely pathogenic (score 0.8919) — an in-silico prediction, not a clinical call.

CAV3 p.Pro29His

c.86C>A · rs116840786 · VCV1463693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.8919	likely pathogenic
REVEL	0.909	moderately pathogenic-leaning
SaProt	LLR -11.34	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 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 12 kb · p 0.021 · regional, not allelic
Overall
CADD	27.9	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 0.00017% European (non-Finnish) · 2/1,177,466 alleles

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

Overall 0.000137% 2/1,459,002 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.Pro29His
Coding: c.86C>A
MANE Select: NM_033337
dbSNP: rs116840786
Type: single nucleotide variant
Location: chr3:8733962 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 88.54
Residue 29: a UniProt-annotated variant site (in hypck)

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.Pro29Leu Uncertain significance ★ ⚠ same residue
CAV3 p.Pro29Ser 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 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-pro29his (accessed [today's date]).

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