Is CACNB2 p.Ile173Val (c.517A>G) pathogenic?

CACNB2 p.Ile173Val (c.517A>G) is classified Uncertain significance in CACNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-09). AlphaMissense: ambiguous (0.4333); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with CACNB2 p.Ile173Val (c.517A>G)?

CACNB2 p.Ile173Val (c.517A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is CACNB2 p.Ile173Val (c.517A>G) in the general population?

CACNB2 p.Ile173Val (c.517A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CACNB2 p.Ile173Val (c.517A>G)?

AlphaMissense predicts ambiguous (score 0.4333) — an in-silico prediction, not a clinical call.

CACNB2 p.Ile173Val

c.517A>G · rs2494363496 · VCV1732671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4333 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4333	ambiguous
REVEL	0.419	indeterminate
SaProt	LLR -9.92	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.79, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 399 kb · p 0.0029 · regional, not allelic
Overall
CADD	22.7	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: CACNB2
Protein: p.Ile173Val
Coding: c.517A>G
MANE Select: NM_201596
dbSNP: rs2494363496
Type: single nucleotide variant
Location: chr10:18500872 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.78 · 3 PDB
Residue 173: the sh3 domain

Full CACNB2 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

CACNB2 c.1206+5G>A Uncertain significance ★★ same condition
CACNB2 c.1303-3C>T Uncertain significance ★★ same condition
CACNB2 p.Ala105Thr Uncertain significance ★★ ⚠ same condition
CACNB2 p.Ala118Val Uncertain significance ★★ ⚠ same condition
CACNB2 p.Ala128Val Uncertain significance ★★ ⚠ same condition
CACNB2 p.Ala139Ser Uncertain significance ★★ ⚠ same condition
CACNB2 p.Ala229Asp Uncertain significance ★★ ⚠ same condition
CACNB2 p.Ala352= 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/cacnb2-p-ile173val (accessed [today's date]).

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