Is ITPR1 p.Arg65= (c.195C>G) pathogenic?

ITPR1 p.Arg65= (c.195C>G) is classified Benign in ITPR1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.52%, sas); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Arg65= (c.195C>G)?

ITPR1 p.Arg65= (c.195C>G) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Arg65= (c.195C>G) in the general population?

ITPR1 p.Arg65= (c.195C>G) is low-frequency (popmax 1.52%, sas) (gnomAD).

ITPR1 p.Arg65=

c.195C>G · rs563347395 · VCV345544

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.52%, sas)

Conditions

autosomal dominant cerebellar ataxia

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 0.55	GERP 0.31, phastCons 0.99
Overall
CADD	9.305	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.52% South Asian · 1,384/91,040 alleles

Filtering AF 1.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.43%

Overall 0.0913% 1,473/1,613,640 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.52%	66
Remaining individualsnot grpmax-eligible	0.072%	1,388
Middle Eastern	0.0495%	2,020
African / African-American	0.00533%	18,746
European (non-Finnish)	0.00314%	31,884

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.Arg65=
Coding: c.195C>G
MANE Select: NM_001378452
dbSNP: rs563347395
Type: single nucleotide variant
Location: chr3:4627794 (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 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
ITPR1 p.Met2750Val Uncertain significance ★★ same condition
ITPR1 p.Ser2180Asn 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-arg65 (accessed [today's date]).

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