Is ITPR3 p.Arg53= (c.159T>C) pathogenic?

ITPR3 p.Arg53= (c.159T>C) is classified Likely benign in ITPR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-11). Rare (popmax 0.565%, afr); Associated with ITPR3-related disorder.

What condition is associated with ITPR3 p.Arg53= (c.159T>C)?

ITPR3 p.Arg53= (c.159T>C) is associated with ITPR3-related disorder (ClinVar).

How common is ITPR3 p.Arg53= (c.159T>C) in the general population?

ITPR3 p.Arg53= (c.159T>C) is rare (popmax 0.565%, afr) (gnomAD).

ITPR3 p.Arg53=

c.159T>C · rs141783150 · VCV3040710

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.565%, afr)

Conditions

ITPR3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.5, phastCons 1
Overall
CADD	15.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.565% African / African-American · 423/74,894 alleles

Filtering AF 0.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.503%

Overall 0.0284% 458/1,611,814 alleles · rare exomes 233/1,459,596 · genomes 225/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.565%	177
Remaining individualsnot grpmax-eligible	0.0305%	3,284
Admixed American	0.0184%	5,425
East Asian	0.00223%	44,782
South Asian	0.0011%	90,828
European (non-Finnish)	0.000254%	392,960

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: ITPR3
Protein: p.Arg53=
Coding: c.159T>C
MANE Select: NM_002224
dbSNP: rs141783150
Type: single nucleotide variant
Location: chr6:33640553 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.04 · 24 PDB
Residue 53: an α-helix

Full ITPR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ITPR3-related disorder

Similar variants

ITPR3 p.Arg53Cys Uncertain significance ★ ⚠ same residue
ITPR3 p.Arg2524Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
ITPR3 c.283-9T>A Uncertain significance same condition
ITPR3 p.Ala1530Pro Uncertain significance ⚠ same condition
ITPR3 p.Gly1812Ser Uncertain significance ⚠ same condition
ITPR3 p.Gly919Cys Uncertain significance ⚠ same condition
ITPR3 p.Ile1969Met Uncertain significance ⚠ same condition
ITPR3 p.Ser120Arg 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/itpr3-p-arg53 (accessed [today's date]).

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