Is ITPR1 p.Asp2503= (c.7509T>C) pathogenic?

ITPR1 p.Asp2503= (c.7509T>C) is classified Benign/Likely benign in ITPR1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-12). Rare (popmax 0.67%, afr); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Asp2503= (c.7509T>C)?

ITPR1 p.Asp2503= (c.7509T>C) is associated with autosomal dominant cerebellar ataxia, spinocerebellar ataxia type 29, aniridia-cerebellar ataxia-intellectual disability syndrome (ClinVar).

How common is ITPR1 p.Asp2503= (c.7509T>C) in the general population?

ITPR1 p.Asp2503= (c.7509T>C) is rare (popmax 0.67%, afr) (gnomAD).

ITPR1 p.Asp2503=

c.7509T>C · rs79720149 · VCV345782

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.67%, afr)

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	all four deltas below 0.2 · T>G here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.4	GERP -2.9
Overall
CADD	0.967	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.67% African / African-American · 503/75,044 alleles

Filtering AF 0.622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.603%

Overall 0.0345% 557/1,613,998 alleles · rare exomes 286/1,461,690 · genomes 271/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.67%	149
Admixed American	0.035%	2,858
Remaining individualsnot grpmax-eligible	0.0224%	4,463
South Asian	0.00439%	22,771
East Asian	0.00223%	44,894
European (non-Finnish)	0.00119%	84,277

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.Asp2503=
Coding: c.7509T>C
MANE Select: NM_001378452
dbSNP: rs79720149
Type: single nucleotide variant
Location: chr3:4813182 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2503: the 'interaction with erp44' 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

Also linked: spinocerebellar ataxia type 29 aniridia-cerebellar ataxia-intellectual disability syndrome spinocerebellar ataxia type 15/16

Similar variants

ITPR1 p.Asp2503Asn Uncertain significance ★ ⚠ same residue
ITPR1 p.Arg241Lys Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Arg269Trp Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Arg504Gly Likely pathogenic ★★ same condition
ITPR1 p.Arg506Trp Likely pathogenic ★★ same condition
ITPR1 p.Arg511Gly Likely pathogenic ★★ same condition
ITPR1 p.Arg511Ser Likely pathogenic ★★ same condition
ITPR1 p.Gly2554Arg Pathogenic/Likely pathogenic ★★ 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-asp2503 (accessed [today's date]).

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