Is CAV3 p.Arg27Pro (c.80G>C) pathogenic?

CAV3 p.Arg27Pro (c.80G>C) is classified Conflicting classifications of pathogenicity in CAV3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-02-16). AlphaMissense: likely pathogenic (0.9943); Absent from gnomAD v4.1; Associated with CAV3-related disorder.

What condition is associated with CAV3 p.Arg27Pro (c.80G>C)?

CAV3 p.Arg27Pro (c.80G>C) is associated with CAV3-related disorder, long QT syndrome (ClinVar).

How common is CAV3 p.Arg27Pro (c.80G>C) in the general population?

CAV3 p.Arg27Pro (c.80G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAV3 p.Arg27Pro (c.80G>C)?

AlphaMissense predicts likely pathogenic (score 0.9943) — an in-silico prediction, not a clinical call.

CAV3 p.Arg27Pro

c.80G>C · rs116840778 · VCV31747

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9943 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CAV3-related disorder

Computational evidence

Protein change
AlphaMissense	0.9943	likely pathogenic · top 2% in CAV3
REVEL	0.953	strongly pathogenic-leaning
SaProt	LLR -14.46	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 12	GERP 2.5, 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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAV3
Protein: p.Arg27Pro
Coding: c.80G>C
MANE Select: NM_033337
dbSNP: rs116840778
Type: single nucleotide variant
Location: chr3:8733956 (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

CAV3-related disorder

Also linked: long QT syndrome

Similar variants

CAV3 p.Arg27Gln Pathogenic ★★ same residue
CAV3 p.Arg27Gly Pathogenic ★ same residue
CAV3 p.Arg27Ter Pathogenic ★ 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-arg27pro (accessed [today's date]).

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