Is ITPR2 p.Val795Met (c.2383G>A) pathogenic?

ITPR2 p.Val795Met (c.2383G>A) is classified Uncertain significance in ITPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: ambiguous (0.4113); Very rare (popmax 0.004%, afr).

How common is ITPR2 p.Val795Met (c.2383G>A) in the general population?

ITPR2 p.Val795Met (c.2383G>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about ITPR2 p.Val795Met (c.2383G>A)?

AlphaMissense predicts ambiguous (score 0.4113) — an in-silico prediction, not a clinical call.

ITPR2 p.Val795Met

c.2383G>A · VCV4680142

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4113 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Computational evidence

Protein change
AlphaMissense	0.4113	ambiguous
REVEL	0.618	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 61 kb · p 0.0071 · regional, not allelic
Overall
CADD	31.0	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 0.004% African / African-American · 3/74,928 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00217% 35/1,614,080 alleles · very rare exomes 31/1,461,886 · genomes 4/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,976
Admixed American	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)	0.0022%	45,386
Finnishnot grpmax-eligible	0.00156%	64,040
South Asian	0.0011%	91,090

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.Val795Met
Coding: c.2383G>A
MANE Select: NM_002223
Type: single nucleotide variant
Location: chr12:26656358 (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-val795met (accessed [today's date]).

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