Is ITPR2 p.Arg344Ser (c.1030C>A) pathogenic?

ITPR2 p.Arg344Ser (c.1030C>A) is classified Uncertain significance in ITPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). AlphaMissense: ambiguous (0.359); Very rare (popmax 0.00401%, afr).

How common is ITPR2 p.Arg344Ser (c.1030C>A) in the general population?

ITPR2 p.Arg344Ser (c.1030C>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about ITPR2 p.Arg344Ser (c.1030C>A)?

AlphaMissense predicts ambiguous (score 0.359) — an in-silico prediction, not a clinical call.

ITPR2 p.Arg344Ser

c.1030C>A · VCV3286994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.359 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Computational evidence

Protein change
AlphaMissense	0.359	ambiguous
REVEL	0.502	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.20	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 8.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 175 kb · p 1.6e-22 · regional, not allelic
Overall
CADD	22.6	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 0.00401% African / African-American · 3/74,720 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000435% 7/1,610,428 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,907
South Asian	0.00331%	30,197
Remaining individualsnot grpmax-eligible	0.00161%	62,304

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.Arg344Ser
Coding: c.1030C>A
MANE Select: NM_002223
Type: single nucleotide variant
Location: chr12:26686599 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Residue 344: the mir 4 domain

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

Similar variants

ITPR2 p.Arg344His 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-arg344ser (accessed [today's date]).

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