Is ITPR2 p.Ile892Val (c.2674A>G) pathogenic?

ITPR2 p.Ile892Val (c.2674A>G) is classified Uncertain significance in ITPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: ambiguous (0.4599); Ultra-rare (popmax 0.0333%, nfe).

How common is ITPR2 p.Ile892Val (c.2674A>G) in the general population?

ITPR2 p.Ile892Val (c.2674A>G) is ultra-rare (popmax 0.0333%, nfe) (gnomAD).

What do computational predictors say about ITPR2 p.Ile892Val (c.2674A>G)?

AlphaMissense predicts ambiguous (score 0.4599) — an in-silico prediction, not a clinical call.

ITPR2 p.Ile892Val

c.2674A>G · VCV3861883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4599 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4599	ambiguous
REVEL	0.685	pathogenic-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 61 kb · p 0.0071 · regional, not allelic
Overall
CADD	25.6	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 0.0333% European (non-Finnish) · 390/1,171,572 alleles

Filtering AF 0.0305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0295%

Overall 0.0254% 406/1,595,376 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0333%	3,004
Remaining individualsnot grpmax-eligible	0.0114%	8,808
African / African-American	0.0109%	9,175
Finnishnot grpmax-eligible	0.00159%	63,030

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.Ile892Val
Coding: c.2674A>G
MANE Select: NM_002223
Type: single nucleotide variant
Location: chr12:26654042 (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.Ile892Thr Uncertain significance ★ ⚠ same residue
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

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-ile892val (accessed [today's date]).

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