Is CACNB1 p.Val244Phe (c.730G>T) pathogenic?

CACNB1 p.Val244Phe (c.730G>T) is classified Uncertain significance in CACNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-01). AlphaMissense: likely pathogenic (0.9984); Absent from gnomAD v4.1.

How common is CACNB1 p.Val244Phe (c.730G>T) in the general population?

CACNB1 p.Val244Phe (c.730G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CACNB1 p.Val244Phe (c.730G>T)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

CACNB1 p.Val244Phe

c.730G>T · rs1597699484 · VCV808256

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9984 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic · top 8% in CACNB1
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -13.43	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 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 22 kb · p 2.7e-10 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CACNB1
Protein: p.Val244Phe
Coding: c.730G>T
MANE Select: NM_000723
dbSNP: rs1597699484
Type: single nucleotide variant
Location: chr17:39184383 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.58 (gnomAD)
Structure: AlphaFold pLDDT 69.79 · 6 PDB
Residue 244: an α-helix

Full CACNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CACNB1 p.Arg487= Benign ★★ same type
CACNB1 p.Ser464= Benign ★★ same type
CACNB1 p.Ala323Gly Uncertain significance ★ same type
CACNB1 p.Ala330Thr Uncertain significance ★ ⚠ same type
CACNB1 p.Ala372Val Uncertain significance ★ ⚠ same type
CACNB1 p.Ala407Thr Uncertain significance ★ ⚠ same type
CACNB1 p.Ala543Asp Uncertain significance ★ ⚠ same type
CACNB1 p.Ala80Gly Uncertain significance ★ ⚠ same type

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/cacnb1-p-val244phe (accessed [today's date]).

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