Is CACNB3 p.Ser241Ala (c.721T>G) pathogenic?

CACNB3 p.Ser241Ala (c.721T>G) is classified Uncertain significance in CACNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: likely benign (0.1048); Absent from gnomAD v4.1.

How common is CACNB3 p.Ser241Ala (c.721T>G) in the general population?

CACNB3 p.Ser241Ala (c.721T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CACNB3 p.Ser241Ala (c.721T>G)?

AlphaMissense predicts likely benign (score 0.1048) — an in-silico prediction, not a clinical call.

CACNB3 p.Ser241Ala

c.721T>G · rs2498725574 · VCV3136498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1048 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1048	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -11.15	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 8,966 bp · p 1e-09 · regional, not allelic
Overall
CADD	26.3	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: CACNB3
Protein: p.Ser241Ala
Coding: c.721T>G
MANE Select: NM_000725
dbSNP: rs2498725574
Type: single nucleotide variant
Location: chr12:48825748 (GRCh38)
Gene constraint: LOEUF 0.722 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.21 · 16 PDB
Residue 241: the 'mediates interaction with the alpha subunit' region; a turn

Full CACNB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CACNB3 p.Ala199Ser Uncertain significance ★ ⚠ same type
CACNB3 p.Ala199Val Uncertain significance ★ ⚠ same type
CACNB3 p.Ala63Val Uncertain significance ★ ⚠ same type
CACNB3 p.Arg107Trp Uncertain significance ★ ⚠ same type
CACNB3 p.Arg123Cys Uncertain significance ★ ⚠ same type
CACNB3 p.Arg123His Uncertain significance ★ ⚠ same type
CACNB3 p.Arg123Ser Uncertain significance ★ ⚠ same type
CACNB3 p.Arg150Gln 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/cacnb3-p-ser241ala (accessed [today's date]).

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