Is CAV3 p.Ile13Val (c.37A>G) pathogenic?

CAV3 p.Ile13Val (c.37A>G) is classified Uncertain significance in CAV3 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-06-21). AlphaMissense: likely benign (0.0757); Very rare (popmax 0.000763%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with CAV3 p.Ile13Val (c.37A>G)?

CAV3 p.Ile13Val (c.37A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is CAV3 p.Ile13Val (c.37A>G) in the general population?

CAV3 p.Ile13Val (c.37A>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about CAV3 p.Ile13Val (c.37A>G)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

CAV3 p.Ile13Val

c.37A>G · rs796052171 · VCV2452813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.385	indeterminate
SaProt	LLR -5.98	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 9.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 12 kb · p 0.021 · regional, not allelic
Overall
CADD	21.0	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 0.000763% European (non-Finnish) · 9/1,179,458 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,282 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.Ile13Val
Coding: c.37A>G
MANE Select: NM_033337
dbSNP: rs796052171
Type: single nucleotide variant
Location: chr3:8733913 (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

Similar variants

CAV3 p.Ile13= Benign/Likely benign ★★ same residue
CAV3 p.Ile13Phe Likely pathogenic ⚠ same residue
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
CAV3 p.Ala93Ser Uncertain significance ★★ ⚠ same condition
CAV3 p.Arg126Cys 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-ile13val (accessed [today's date]).

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