Is ITPR1 p.Arg36His (c.107G>A) pathogenic?

ITPR1 p.Arg36His (c.107G>A) is classified Conflicting classifications of pathogenicity in ITPR1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2022-11-29). AlphaMissense: likely pathogenic (0.9715); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ITPR1 p.Arg36His (c.107G>A)?

ITPR1 p.Arg36His (c.107G>A) is associated with Inborn genetic diseases, spinocerebellar ataxia type 29 (ClinVar).

How common is ITPR1 p.Arg36His (c.107G>A) in the general population?

ITPR1 p.Arg36His (c.107G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ITPR1 p.Arg36His (c.107G>A)?

AlphaMissense predicts likely pathogenic (score 0.9715) — an in-silico prediction, not a clinical call.

ITPR1 p.Arg36His

c.107G>A · rs1057518026 · VCV372854

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9715	likely pathogenic
REVEL	0.86	moderately pathogenic-leaning
SaProt	LLR -11.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 129 kb · p 1.8e-14 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,186 alleles

Overall 6.2e-05% 1/1,613,156 alleles · very rare exomes 1/1,460,882 · genomes 0/152,274 · 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.Arg36His
Coding: c.107G>A
MANE Select: NM_001378452
dbSNP: rs1057518026
Type: single nucleotide variant
Location: chr3:4521038 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spinocerebellar ataxia type 29

Similar variants

ITPR1 p.Arg36Cys Conflicting classifications of pathogenicity ★ ⚠ 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.Arg511Gly Likely pathogenic ★★ same condition
ITPR1 p.Arg511Ser Likely pathogenic ★★ same condition
ITPR1 p.Gly2554Arg Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Ile2598Thr 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-arg36his (accessed [today's date]).

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