Is ITPR1 p.Val433Ile (c.1297G>A) pathogenic?

ITPR1 p.Val433Ile (c.1297G>A) is classified Uncertain significance in ITPR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1327); Absent from gnomAD v4.1; Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Val433Ile (c.1297G>A)?

ITPR1 p.Val433Ile (c.1297G>A) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Val433Ile (c.1297G>A) in the general population?

ITPR1 p.Val433Ile (c.1297G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITPR1 p.Val433Ile (c.1297G>A)?

AlphaMissense predicts likely benign (score 0.1327) — an in-silico prediction, not a clinical call.

ITPR1 p.Val433Ile

c.1297G>A · rs2093848251 · VCV899718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1327 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal dominant cerebellar ataxia

Computational evidence

Protein change
AlphaMissense	0.1327	likely benign
REVEL	0.42	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.15	constrained · MANE · 47 bp · p 0.00012 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ITPR1
Protein: p.Val433Ile
Coding: c.1297G>A
MANE Select: NM_001378452
dbSNP: rs2093848251
Type: single nucleotide variant
Location: chr3:4662127 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 433: the mir 5 domain

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.Val433Phe 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-val433ile (accessed [today's date]).

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