Is ITPR2 p.Arg799His (c.2396G>A) pathogenic?

ITPR2 p.Arg799His (c.2396G>A) is classified Uncertain significance in ITPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: ambiguous (0.3685); Ultra-rare (popmax 0.0467%, afr).

How common is ITPR2 p.Arg799His (c.2396G>A) in the general population?

ITPR2 p.Arg799His (c.2396G>A) is ultra-rare (popmax 0.0467%, afr) (gnomAD).

What do computational predictors say about ITPR2 p.Arg799His (c.2396G>A)?

AlphaMissense predicts ambiguous (score 0.3685) — an in-silico prediction, not a clinical call.

ITPR2 p.Arg799His

c.2396G>A · rs372497705 · VCV3111754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3685 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, afr)

Computational evidence

Protein change
AlphaMissense	0.3685	ambiguous
REVEL	0.369	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 61 kb · p 0.0071 · regional, not allelic
Overall
CADD	27.5	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 0.0467% African / African-American · 35/74,908 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0303%

Overall 0.00254% 41/1,614,050 alleles · ultra-rare exomes 16/1,461,886 · genomes 25/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0467%	2,140
Admixed American	0.005%	20,003
European (non-Finnish)	0.000254%	393,348

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.Arg799His
Coding: c.2396G>A
MANE Select: NM_002223
dbSNP: rs372497705
Type: single nucleotide variant
Location: chr12:26656345 (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.Arg799Cys 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-arg799his (accessed [today's date]).

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