Is ITPR2 p.Val964= (c.2892G>A) pathogenic?

ITPR2 p.Val964= (c.2892G>A) is classified Likely benign in ITPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). Rare (popmax 0.454%, sas).

How common is ITPR2 p.Val964= (c.2892G>A) in the general population?

ITPR2 p.Val964= (c.2892G>A) is rare (popmax 0.454%, sas) (gnomAD).

ITPR2 p.Val964=

c.2892G>A · VCV4916007

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.454%, sas)

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 -0.36	GERP -3.5, phastCons 0.085
Overall
CADD	6.277	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.454% South Asian · 413/91,060 alleles

Filtering AF 0.417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.403%

Overall 0.051% 823/1,614,080 alleles · rare exomes 755/1,461,828 · genomes 68/152,252 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.554%	180
South Asiangrpmax	0.454%	220
Middle Eastern	0.214%	466
Remaining individualsnot grpmax-eligible	0.064%	1,563
Admixed American	0.02%	5,001
European (non-Finnish)	0.0148%	6,743
African / African-American	0.00533%	18,755
East Asian	0.00446%	22,433

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val964=
Coding: c.2892G>A
MANE Select: NM_002223
Type: single nucleotide variant
Location: chr12:26631908 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)

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-val964 (accessed [today's date]).

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