Is ITPR1 p.Arg623= (c.1867C>A) pathogenic?

ITPR1 p.Arg623= (c.1867C>A) is classified Uncertain significance in ITPR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). Very rare (popmax 0.00314%, nfe); Associated with aniridia-cerebellar ataxia-intellectual disability syndrome.

What condition is associated with ITPR1 p.Arg623= (c.1867C>A)?

ITPR1 p.Arg623= (c.1867C>A) is associated with aniridia-cerebellar ataxia-intellectual disability syndrome (ClinVar).

How common is ITPR1 p.Arg623= (c.1867C>A) in the general population?

ITPR1 p.Arg623= (c.1867C>A) is very rare (popmax 0.00314%, nfe) (gnomAD).

ITPR1 p.Arg623=

c.1867C>A · VCV3773793

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Conditions

aniridia-cerebellar ataxia-intellectual disability syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.89	donor gain · deltas
Pangolin	Δ0.65	gain · loss 0.22 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.3	GERP 1.9, phastCons 1
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00314% European (non-Finnish) · 37/1,179,420 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00236% 38/1,612,870 alleles · very rare exomes 35/1,460,760 · genomes 3/152,110 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,876
African / African-American	0.00134%	74,860

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.Arg623=
Coding: c.1867C>A
MANE Select: NM_001378452
Type: single nucleotide variant
Location: chr3:4667530 (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

aniridia-cerebellar ataxia-intellectual disability syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITPR1 p.Arg623Ter Pathogenic ★ same residue
ITPR1 p.Arg269Trp Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Arg506Trp Likely pathogenic ★★ same condition
ITPR1 p.Gly2554Arg Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Tyr567Cys Pathogenic ★★ same condition
ITPR1 p.Val1445Met Likely pathogenic ★★ same condition
ITPR1 p.Ala1222Thr Uncertain significance ★★ ⚠ same condition
ITPR1 p.Ala1480Thr 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-arg623 (accessed [today's date]).

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