Is CACNB4 p.Ser264= (c.792T>C) pathogenic?

CACNB4 p.Ser264= (c.792T>C) is classified Benign/Likely benign in CACNB4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-10-07). Rare (popmax 0.381%, afr); Associated with idiopathic generalized epilepsy.

What condition is associated with CACNB4 p.Ser264= (c.792T>C)?

CACNB4 p.Ser264= (c.792T>C) is associated with idiopathic generalized epilepsy (ClinVar).

How common is CACNB4 p.Ser264= (c.792T>C) in the general population?

CACNB4 p.Ser264= (c.792T>C) is rare (popmax 0.381%, afr) (gnomAD).

CACNB4 p.Ser264=

c.792T>C · rs139448267 · VCV204922

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.381%, afr)

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Overall
CADD	12.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.381% African / African-American · 286/75,050 alleles

Filtering AF 0.345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.331%

Overall 0.0186% 300/1,613,530 alleles · rare exomes 137/1,461,200 · genomes 163/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.381%	262
Remaining individualsnot grpmax-eligible	0.0128%	7,808
Admixed American	0.00833%	12,006
South Asian	0.0011%	91,068

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: CACNB4
Protein: p.Ser264=
Coding: c.792T>C
MANE Select: NM_000726
dbSNP: rs139448267
Type: single nucleotide variant
Location: chr2:151860787 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.29 · 1 PDB

Full CACNB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

idiopathic generalized epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CACNB4 p.Ala12Ser Uncertain significance ★★ ⚠ same condition
CACNB4 p.Arg437Ter Uncertain significance ★★ same condition
CACNB4 p.Arg453Leu Uncertain significance ★★ ⚠ same condition
CACNB4 p.Arg473Cys Uncertain significance ★★ same condition
CACNB4 p.Arg473His Uncertain significance ★★ ⚠ same condition
CACNB4 p.Arg517Gln Uncertain significance ★★ ⚠ same condition
CACNB4 p.Arg517Ter Uncertain significance ★★ same condition
CACNB4 p.Gln343Glu 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/cacnb4-p-ser264 (accessed [today's date]).

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