Is ITPR2 p.Asp321Gly (c.962A>G) pathogenic?

ITPR2 p.Asp321Gly (c.962A>G) is classified Uncertain significance in ITPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.1063); Ultra-rare (popmax 0.0374%, sas).

How common is ITPR2 p.Asp321Gly (c.962A>G) in the general population?

ITPR2 p.Asp321Gly (c.962A>G) is ultra-rare (popmax 0.0374%, sas) (gnomAD).

What do computational predictors say about ITPR2 p.Asp321Gly (c.962A>G)?

AlphaMissense predicts likely benign (score 0.1063) — an in-silico prediction, not a clinical call.

ITPR2 p.Asp321Gly

c.962A>G · VCV4833657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1063 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0374%, sas)

Computational evidence

Protein change
AlphaMissense	0.1063	likely benign
REVEL	0.388	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 175 kb · p 1.6e-22 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0374% South Asian · 34/91,002 alleles

Filtering AF 0.0274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.024%

Overall 0.00217% 35/1,612,704 alleles · ultra-rare exomes 32/1,460,440 · genomes 3/152,264 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0374%	2,677
Remaining individualsnot grpmax-eligible	0.0016%	62,448

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: ITPR2
Protein: p.Asp321Gly
Coding: c.962A>G
MANE Select: NM_002223
Type: single nucleotide variant
Location: chr12:26695640 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Residue 321: the mir 4 domain

Full ITPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ITPR2 p.Val1162Gly Uncertain significance ★★ same type
ITPR2 c.3801+23G>A Benign ★★ same type
ITPR2 c.5073+10T>A Benign ★★ same type
ITPR2 c.93-10T>A Benign ★★ same type
ITPR2 p.Ala1898Val Benign ★★ same type
ITPR2 p.Arg1180Gln Likely benign ★★ same type
ITPR2 p.Arg1275Gln Likely benign ★★ same type
ITPR2 p.Asn461= Benign ★★ same type

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/itpr2-p-asp321gly (accessed [today's date]).

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