Is ITPR3 p.Ser120Arg (c.360T>G) pathogenic?

ITPR3 p.Ser120Arg (c.360T>G) is classified Uncertain significance in ITPR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely pathogenic (0.8259); Absent from gnomAD v4.1; Associated with ITPR3-related disorder.

What condition is associated with ITPR3 p.Ser120Arg (c.360T>G)?

ITPR3 p.Ser120Arg (c.360T>G) is associated with ITPR3-related disorder (ClinVar).

How common is ITPR3 p.Ser120Arg (c.360T>G) in the general population?

ITPR3 p.Ser120Arg (c.360T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITPR3 p.Ser120Arg (c.360T>G)?

AlphaMissense predicts likely pathogenic (score 0.8259) — an in-silico prediction, not a clinical call.

ITPR3 p.Ser120Arg

c.360T>G · VCV3354652

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8259 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ITPR3-related disorder

Computational evidence

Protein change
AlphaMissense	0.8259	likely pathogenic
REVEL	0.636	indeterminate
SaProt	LLR -10.75	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.6	GERP -4.7
Regional constraint	o/e 0.62	unconstrained · MANE · 6,740 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	14.96	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

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: ITPR3
Protein: p.Ser120Arg
Coding: c.360T>G
MANE Select: NM_002224
Type: single nucleotide variant
Location: chr6:33658009 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.04 · 24 PDB
Residue 120: the mir 1 domain

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

Disease context

ITPR3-related disorder

Similar variants

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 c.3282+6G>A Likely benign same condition
ITPR3 c.3771+8T>C Benign 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-ser120arg (accessed [today's date]).

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