Is ITPR3 p.Ser1843= (c.5529G>T) pathogenic?

ITPR3 p.Ser1843= (c.5529G>T) is classified Uncertain significance in ITPR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-16). No allele count reported in gnomAD v4.1 (AN 1,601,976); Associated with Charcot-Marie-Tooth disease, demyelinating, type 1J.

What condition is associated with ITPR3 p.Ser1843= (c.5529G>T)?

ITPR3 p.Ser1843= (c.5529G>T) is associated with Charcot-Marie-Tooth disease, demyelinating, type 1J (ClinVar).

How common is ITPR3 p.Ser1843= (c.5529G>T) in the general population?

ITPR3 p.Ser1843= (c.5529G>T) is no allele count reported in gnomAD v4.1 (AN 1,601,976) (gnomAD).

ITPR3 p.Ser1843=

c.5529G>T · VCV4537368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,601,976)

Conditions

Charcot-Marie-Tooth disease, demyelinating, type 1J

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.60	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -3.7	GERP -3.5
Overall
CADD	14.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,601,976). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ITPR3
Protein: p.Ser1843=
Coding: c.5529G>T
MANE Select: NM_002224
Type: single nucleotide variant
Location: chr6:33685689 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.04 · 24 PDB
Residue 1843: the 'disordered' region

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

Disease context

Charcot-Marie-Tooth disease, demyelinating, type 1J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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.Asp1968Val 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

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-ser1843 (accessed [today's date]).

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