Is ITPR3 p.Asn460= (c.1380C>T) pathogenic?

ITPR3 p.Asn460= (c.1380C>T) is classified Likely benign in ITPR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-01). Ultra-rare (popmax 0.0913%, eas); Associated with ITPR3-related disorder.

What condition is associated with ITPR3 p.Asn460= (c.1380C>T)?

ITPR3 p.Asn460= (c.1380C>T) is associated with ITPR3-related disorder (ClinVar).

How common is ITPR3 p.Asn460= (c.1380C>T) in the general population?

ITPR3 p.Asn460= (c.1380C>T) is ultra-rare (popmax 0.0913%, eas) (gnomAD).

ITPR3 p.Asn460=

c.1380C>T · rs780808015 · VCV3050443

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0913%, eas)

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 -13	GERP -5
Overall
CADD	1.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0913% East Asian · 41/44,898 alleles

Filtering AF 0.0692% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0614%

Overall 0.00905% 146/1,613,984 alleles · ultra-rare exomes 133/1,461,732 · genomes 13/152,252 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0913%	1,095
South Asian	0.0549%	1,822
European (non-Finnish)	0.00424%	23,600
Remaining individualsnot grpmax-eligible	0.0032%	31,241
African / African-American	0.00267%	37,474
Admixed American	0.00167%	60,012

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.Asn460=
Coding: c.1380C>T
MANE Select: NM_002224
dbSNP: rs780808015
Type: single nucleotide variant
Location: chr6:33665184 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.04 · 24 PDB
Residue 460: 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.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
ITPR3 c.3282+6G>A Likely 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-asn460 (accessed [today's date]).

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