Is ITPR1 p.Arg1595= (c.4785C>T) pathogenic?

ITPR1 p.Arg1595= (c.4785C>T) is classified Uncertain significance in ITPR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00445%, eas); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Arg1595= (c.4785C>T)?

ITPR1 p.Arg1595= (c.4785C>T) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Arg1595= (c.4785C>T) in the general population?

ITPR1 p.Arg1595= (c.4785C>T) is very rare (popmax 0.00445%, eas) (gnomAD).

ITPR1 p.Arg1595=

c.4785C>T · rs2094755597 · VCV902724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Conditions

autosomal dominant cerebellar ataxia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.029	GERP -3.7, phastCons 0.12
Overall
CADD	8.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,898 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000186% 3/1,613,910 alleles · very rare exomes 2/1,461,668 · genomes 1/152,242 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,449
European (non-Finnish)	8.48e-05%	1,179,876

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.Arg1595=
Coding: c.4785C>T
MANE Select: NM_001378452
dbSNP: rs2094755597
Type: single nucleotide variant
Location: chr3:4706294 (GRCh38)

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

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-arg1595 (accessed [today's date]).

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