Is ITPR1 p.Ala2193= (c.6579C>A) pathogenic?

ITPR1 p.Ala2193= (c.6579C>A) is classified Conflicting classifications of pathogenicity in ITPR1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-31). Ultra-rare (popmax 0.0154%, nfe); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Ala2193= (c.6579C>A)?

ITPR1 p.Ala2193= (c.6579C>A) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Ala2193= (c.6579C>A) in the general population?

ITPR1 p.Ala2193= (c.6579C>A) is ultra-rare (popmax 0.0154%, nfe) (gnomAD).

ITPR1 p.Ala2193=

c.6579C>A · rs35343277 · VCV902787

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, nfe)

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 -6.6	GERP -5.7
Overall
CADD	0.908	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% European (non-Finnish) · 182/1,178,266 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.0117% 188/1,609,848 alleles · ultra-rare exomes 181/1,457,746 · genomes 7/152,102 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0154%	6,474
Remaining individualsnot grpmax-eligible	0.00963%	10,389

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.Ala2193=
Coding: c.6579C>A
MANE Select: NM_001378452
dbSNP: rs35343277
Type: single nucleotide variant
Location: chr3:4783884 (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-ala2193 (accessed [today's date]).

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