Is ITPR3 p.Asp1968Val (c.5903A>T) pathogenic?

ITPR3 p.Asp1968Val (c.5903A>T) is classified Uncertain significance in ITPR3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-06). AlphaMissense: likely pathogenic (0.9964); Absent from gnomAD v4.1; Associated with type 1 diabetes mellitus.

What condition is associated with ITPR3 p.Asp1968Val (c.5903A>T)?

ITPR3 p.Asp1968Val (c.5903A>T) is associated with type 1 diabetes mellitus, Charcot-Marie-Tooth disease, demyelinating, type 1J (ClinVar).

How common is ITPR3 p.Asp1968Val (c.5903A>T) in the general population?

ITPR3 p.Asp1968Val (c.5903A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITPR3 p.Asp1968Val (c.5903A>T)?

AlphaMissense predicts likely pathogenic (score 0.9964) — an in-silico prediction, not a clinical call.

ITPR3 p.Asp1968Val

c.5903A>T · VCV3360604

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9964 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

type 1 diabetes mellitus

Computational evidence

Protein change
AlphaMissense	0.9964	likely pathogenic · top 6% in ITPR3
REVEL	0.941	strongly pathogenic-leaning
SaProt	LLR -11.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 6,885 bp · p 0.00093 · regional, not allelic
Overall
CADD	27.7	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.Asp1968Val
Coding: c.5903A>T
MANE Select: NM_002224
Type: single nucleotide variant
Location: chr6:33686443 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.04 · 24 PDB
Residue 1968: an α-helix

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

Disease context

type 1 diabetes mellitus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease, demyelinating, type 1J

Similar variants

ITPR3 p.Thr1424Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
ITPR3 p.Ala1352Thr Uncertain significance ★★ ⚠ same condition
ITPR3 p.Arg1085Leu Uncertain significance ★★ ⚠ same condition
ITPR3 p.Glu669Asp Uncertain significance ★★ ⚠ same condition
ITPR3 p.His359Arg Uncertain significance ★★ ⚠ same condition
ITPR3 p.Arg2524Ser Likely pathogenic ★ same condition
ITPR3 c.5138-8G>A Uncertain significance ★ same condition
ITPR3 p.Arg149Trp Conflicting classifications of pathogenicity ★ ⚠ 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-asp1968val (accessed [today's date]).

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