Is ITPR1 p.Asp2729= (c.8187T>C) pathogenic?

ITPR1 p.Asp2729= (c.8187T>C) is classified Uncertain significance in ITPR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 8.65e-05%, nfe); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Asp2729= (c.8187T>C)?

ITPR1 p.Asp2729= (c.8187T>C) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Asp2729= (c.8187T>C) in the general population?

ITPR1 p.Asp2729= (c.8187T>C) is very rare (popmax 8.65e-05%, nfe) (gnomAD).

ITPR1 p.Asp2729=

c.8187T>C · rs2050964614 · VCV901076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.65e-05%, 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 -2.1	GERP -3.9
Overall
CADD	1.626	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.65e-05% European (non-Finnish) · 1/1,156,704 alleles

Overall 6.32e-05% 1/1,581,466 alleles · very rare exomes 1/1,429,844 · genomes 0/151,622 · joint denominator

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.Asp2729=
Coding: c.8187T>C
MANE Select: NM_001378452
dbSNP: rs2050964614
Type: single nucleotide variant
Location: chr3:4836932 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2729: the 'disordered' region

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-asp2729 (accessed [today's date]).

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