Is ITPR1 p.Ser2497= (c.7491C>T) pathogenic?

ITPR1 p.Ser2497= (c.7491C>T) is classified Conflicting classifications of pathogenicity in ITPR1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-09). Rare (popmax 0.178%, sas); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Ser2497= (c.7491C>T)?

ITPR1 p.Ser2497= (c.7491C>T) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Ser2497= (c.7491C>T) in the general population?

ITPR1 p.Ser2497= (c.7491C>T) is rare (popmax 0.178%, sas) (gnomAD).

ITPR1 p.Ser2497=

c.7491C>T · rs371986594 · VCV902189

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.178%, sas)

Conditions

autosomal dominant cerebellar ataxia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.44	donor gain · deltas
Constraint at this position
Conservation	phyloP -4.6	GERP -2.9
Overall
CADD	14.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.178% South Asian · 162/91,076 alleles

Filtering AF 0.156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.0218% 352/1,613,892 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.178%	562
African / African-American	0.036%	2,778
Middle Eastern	0.0165%	6,048
Remaining individualsnot grpmax-eligible	0.016%	6,248
European (non-Finnish)	0.0123%	8,137
Admixed American	0.0117%	8,574

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.Ser2497=
Coding: c.7491C>T
MANE Select: NM_001378452
dbSNP: rs371986594
Type: single nucleotide variant
Location: chr3:4813164 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2497: 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

Similar variants

ITPR1 p.Ser2497Gly Uncertain significance ★ ⚠ same residue
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

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-ser2497 (accessed [today's date]).

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