Is CACNA1B p.Ala826Val (c.2477C>T) pathogenic?

CACNA1B p.Ala826Val (c.2477C>T) is classified Uncertain significance in CACNA1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-13). AlphaMissense: likely benign (0.0731); Very rare (popmax 0.00517%, eas).

How common is CACNA1B p.Ala826Val (c.2477C>T) in the general population?

CACNA1B p.Ala826Val (c.2477C>T) is very rare (popmax 0.00517%, eas) (gnomAD).

What do computational predictors say about CACNA1B p.Ala826Val (c.2477C>T)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

CACNA1B p.Ala826Val

c.2477C>T · rs1184420674 · VCV1916017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.23	benign-leaning
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	phastCons 0.005
Regional constraint	o/e 1.00	unconstrained · MANE · 34 kb · p 1 · regional, not allelic
Overall
CADD	9.34	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.00517% East Asian · 2/38,716 alleles

Filtering AF 0.000856% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00032%

Overall 0.000265% 4/1,509,778 alleles · very rare exomes 3/1,357,638 · genomes 1/152,140 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00517%	19,358
African / African-American	0.00287%	34,880

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: CACNA1B
Protein: p.Ala826Val
Coding: c.2477C>T
MANE Select: NM_000718
dbSNP: rs1184420674
Type: single nucleotide variant
Location: chr9:138023220 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.66 · 7 PDB
Residue 826: a UniProt-annotated variant site (in nedneh); the 'disordered' region

Full CACNA1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CACNA1B p.Arg2102Ter Pathogenic/Likely pathogenic ★★ same type
CACNA1B p.Ala1161Thr Uncertain significance ★★ ⚠ same type
CACNA1B p.Ala1556Val Uncertain significance ★★ ⚠ same type
CACNA1B p.Ala1999Val Uncertain significance ★★ same type
CACNA1B p.Ala2080Thr Uncertain significance ★★ ⚠ same type
CACNA1B p.Ala2214Thr Uncertain significance ★★ ⚠ same type
CACNA1B p.Ala2237Thr Uncertain significance ★★ ⚠ same type
CACNA1B p.Ala2249Thr 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/cacna1b-p-ala826val (accessed [today's date]).

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