Is ITPR2 p.Met2344Val (c.7030A>G) pathogenic?

ITPR2 p.Met2344Val (c.7030A>G) is classified Uncertain significance in ITPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-10). AlphaMissense: likely benign (0.0593); Very rare (popmax 0.0011%, sas).

How common is ITPR2 p.Met2344Val (c.7030A>G) in the general population?

ITPR2 p.Met2344Val (c.7030A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ITPR2 p.Met2344Val (c.7030A>G)?

AlphaMissense predicts likely benign (score 0.0593) — an in-silico prediction, not a clinical call.

ITPR2 p.Met2344Val

c.7030A>G · VCV3861891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0593 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.0593	likely benign
REVEL	0.363	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP -5.9, phastCons 0.061
Regional constraint	o/e 0.71	unconstrained · MANE · 13 kb · p 0.0021 · regional, not allelic
Overall
CADD	9.31	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 0.0011% South Asian · 1/91,068 alleles

Overall 0.000137% 2/1,461,584 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,068
European (non-Finnish)	8.48e-05%	1,179,844

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.Met2344Val
Coding: c.7030A>G
MANE Select: NM_002223
Type: single nucleotide variant
Location: chr12:26419129 (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-met2344val (accessed [today's date]).

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