Is CACNA1I p.Pro910= (c.2730C>T) pathogenic?

CACNA1I p.Pro910= (c.2730C>T) is classified Likely benign in CACNA1I (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). Very rare (popmax 0.00133%, afr).

How common is CACNA1I p.Pro910= (c.2730C>T) in the general population?

CACNA1I p.Pro910= (c.2730C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

CACNA1I p.Pro910=

c.2730C>T · VCV4687538

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 0.76	GERP -0.56, phastCons 1
Overall
CADD	11.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,922 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,613,368 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,450
African / African-Americangrpmax	0.00133%	74,922
European (non-Finnish)	0.00017%	589,904

Remaining individuals 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: CACNA1I
Protein: p.Pro910=
Coding: c.2730C>T
MANE Select: NM_021096
Type: single nucleotide variant
Location: chr22:39661139 (GRCh38)
Gene constraint: LOEUF 0.525 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.94 · 4 PDB
Residue 910: the 'disordered' region

Full CACNA1I gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CACNA1I p.Arg1131Leu Uncertain significance ★★ ⚠ same type
CACNA1I p.Arg1453Gln Uncertain significance ★★ ⚠ same type
CACNA1I p.Arg1466Trp Uncertain significance ★★ same type
CACNA1I p.Arg2064His Uncertain significance ★★ ⚠ same type
CACNA1I p.Arg791His Uncertain significance ★★ ⚠ same type
CACNA1I p.Arg950Gln Uncertain significance ★★ ⚠ same type
CACNA1I p.Arg965Cys Uncertain significance ★★ ⚠ same type
CACNA1I p.Arg987Cys 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/cacna1i-p-pro910 (accessed [today's date]).

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