Is ITPR1 p.Arg1216= (c.3648G>A) pathogenic?

ITPR1 p.Arg1216= (c.3648G>A) is classified Uncertain significance in ITPR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.147%, eas); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Arg1216= (c.3648G>A)?

ITPR1 p.Arg1216= (c.3648G>A) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Arg1216= (c.3648G>A) in the general population?

ITPR1 p.Arg1216= (c.3648G>A) is rare (popmax 0.147%, eas) (gnomAD).

ITPR1 p.Arg1216=

c.3648G>A · rs540908870 · VCV345729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.147%, eas)

Conditions

autosomal dominant cerebellar ataxia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.9	GERP -1, phastCons 1
Overall
CADD	5.541	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.147% East Asian · 66/44,816 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00416% 67/1,609,268 alleles · rare exomes 65/1,456,904 · genomes 2/152,364 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.147%	679
Remaining individualsnot grpmax-eligible	0.0016%	62,380

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: ITPR1
Protein: p.Arg1216=
Coding: c.3648G>A
MANE Select: NM_001378452
dbSNP: rs540908870
Type: single nucleotide variant
Location: chr3:4685152 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)

Full ITPR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant cerebellar ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITPR1 p.Arg1216Gln Uncertain significance ★★ ⚠ same residue
ITPR1 p.Arg1216Trp Uncertain significance ★★ ⚠ same residue
ITPR1 c.*1531G>A Uncertain significance ★★ same condition
ITPR1 p.Arg1761Gln Uncertain significance ★★ same condition
ITPR1 p.Arg343Lys Uncertain significance ★★ same condition
ITPR1 p.Asp1959Asn Uncertain significance ★★ same condition
ITPR1 p.Glu2128Val Uncertain significance ★★ ⚠ same condition
ITPR1 p.Gly1782Arg 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/itpr1-p-arg1216 (accessed [today's date]).

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