Is ITPR1 p.Arg511Ser (c.1533A>T) pathogenic?

ITPR1 p.Arg511Ser (c.1533A>T) is classified Likely pathogenic in ITPR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-04). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1; Associated with spinocerebellar ataxia type 29.

What condition is associated with ITPR1 p.Arg511Ser (c.1533A>T)?

ITPR1 p.Arg511Ser (c.1533A>T) is associated with spinocerebellar ataxia type 29 (ClinVar).

How common is ITPR1 p.Arg511Ser (c.1533A>T) in the general population?

ITPR1 p.Arg511Ser (c.1533A>T) is absent from gnomAD v4.1 (gnomAD).

How is Spinocerebellar ataxia type 29 inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ITPR1 p.Arg511Ser (c.1533A>T)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

ITPR1 p.Arg511Ser

c.1533A>T · rs2470706402 · VCV3252734

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

spinocerebellar ataxia type 29

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic ✓ concordant with ClinVar · top 2% in ITPR1
REVEL	0.869	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.42	GERP -4.3
Regional constraint	o/e 0.69	unconstrained · MANE · 18 kb · p 1.3e-16 · regional, not allelic
Overall
CADD	18.39	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.Arg511Ser
Coding: c.1533A>T
MANE Select: NM_001378452
dbSNP: rs2470706402
Type: single nucleotide variant
Location: chr3:4663185 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 511: a binding site

Full ITPR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spinocerebellar ataxia type 29 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 29 (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ITPR1 p.Arg511Gly Likely pathogenic ★★ same residue
ITPR1 p.Arg511Lys Likely pathogenic ★ 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.Gly2554Arg Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Ile2598Thr Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Thr2434Ile 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-arg511ser (accessed [today's date]).

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