Is CACNA1B p.Pro262= (c.786C>T) pathogenic?

CACNA1B p.Pro262= (c.786C>T) is classified Likely benign in CACNA1B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0435%, amr).

How common is CACNA1B p.Pro262= (c.786C>T) in the general population?

CACNA1B p.Pro262= (c.786C>T) is ultra-rare (popmax 0.0435%, amr) (gnomAD).

CACNA1B p.Pro262=

c.786C>T · rs199817628 · VCV2187966

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0435%, amr)

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 -10	GERP -4
Overall
CADD	0.558	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0435% Admixed American · 26/59,824 alleles

Filtering AF 0.0304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0261%

Overall 0.0105% 169/1,612,658 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.204%	491
Admixed Americangrpmax	0.0435%	2,301
East Asian	0.0223%	4,489
Remaining individualsnot grpmax-eligible	0.0208%	4,801
Middle Eastern	0.0165%	6,070
European (non-Finnish)	0.00483%	20,689
Finnishnot grpmax-eligible	0.00156%	63,966
African / African-American	0.00134%	74,904

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro262=
Coding: c.786C>T
MANE Select: NM_000718
dbSNP: rs199817628
Type: single nucleotide variant
Location: chr9:137917251 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.66 · 7 PDB

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-pro262 (accessed [today's date]).

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