Is CAV3 p.Asp55Glu (c.165C>A) pathogenic?

CAV3 p.Asp55Glu (c.165C>A) is classified Uncertain significance in CAV3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-09-11). AlphaMissense: likely pathogenic (0.8323); Very rare (popmax 0.00167%, amr); Associated with long QT syndrome.

What condition is associated with CAV3 p.Asp55Glu (c.165C>A)?

CAV3 p.Asp55Glu (c.165C>A) is associated with long QT syndrome, caveolinopathy (ClinVar).

How common is CAV3 p.Asp55Glu (c.165C>A) in the general population?

CAV3 p.Asp55Glu (c.165C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CAV3 p.Asp55Glu (c.165C>A)?

AlphaMissense predicts likely pathogenic (score 0.8323) — an in-silico prediction, not a clinical call.

CAV3 p.Asp55Glu

c.165C>A · rs759446749 · VCV1037574

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8323 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.8323	likely pathogenic
REVEL	0.711	pathogenic-leaning
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.8	GERP -5.3
Regional constraint	o/e 0.83	unconstrained · MANE · 12 kb · p 0.021 · regional, not allelic
Overall
CADD	14.02	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 0.00167% Admixed American · 1/60,020 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,828 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,020
European (non-Finnish)	0.000593%	168,571

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.Asp55Glu
Coding: c.165C>A
MANE Select: NM_033337
dbSNP: rs759446749
Type: single nucleotide variant
Location: chr3:8745576 (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

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: caveolinopathy

Similar variants

CAV3 p.Asp55Asn Uncertain significance ★ ⚠ same residue
CAV3 p.Asp55= Likely benign ★ same residue
CAV3 p.Asp55fs Uncertain significance ★★ same residue
CAV3 p.Asp55Gly 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

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-asp55glu (accessed [today's date]).

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