Is CAV3 p.Val151Ile (c.451G>A) pathogenic?

CAV3 p.Val151Ile (c.451G>A) is classified Conflicting classifications of pathogenicity in CAV3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-07). AlphaMissense: likely benign (0.0756); Ultra-rare (popmax 0.0434%, amr); Associated with Cardiovascular phenotype.

What condition is associated with CAV3 p.Val151Ile (c.451G>A)?

CAV3 p.Val151Ile (c.451G>A) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is CAV3 p.Val151Ile (c.451G>A) in the general population?

CAV3 p.Val151Ile (c.451G>A) is ultra-rare (popmax 0.0434%, amr) (gnomAD).

What do computational predictors say about CAV3 p.Val151Ile (c.451G>A)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

CAV3 p.Val151Ile

c.451G>A · rs780870487 · VCV409257

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0434%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.341	indeterminate
SaProt	LLR -6.79	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 1.3	GERP -4.8, phastCons 0.001
Regional constraint	o/e 0.83	unconstrained · MANE · 12 kb · p 0.021 · regional, not allelic
Overall
CADD	7.193	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 0.0434% Admixed American · 26/59,972 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00168% 27/1,609,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0434%	2,307
Remaining individualsnot grpmax-eligible	0.0016%	62,382

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.Val151Ile
Coding: c.451G>A
MANE Select: NM_033337
dbSNP: rs780870487
Type: single nucleotide variant
Location: chr3:8745862 (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-val151ile (accessed [today's date]).

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