Is ITPR3 p.Asp2428Val (c.7283A>T) pathogenic?

ITPR3 p.Asp2428Val (c.7283A>T) is classified Uncertain significance in ITPR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.1422); Ultra-rare (popmax 0.0825%, mid).

How common is ITPR3 p.Asp2428Val (c.7283A>T) in the general population?

ITPR3 p.Asp2428Val (c.7283A>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

What do computational predictors say about ITPR3 p.Asp2428Val (c.7283A>T)?

AlphaMissense predicts likely benign (score 0.1422) — an in-silico prediction, not a clinical call.

ITPR3 p.Asp2428Val

c.7283A>T · rs531503671 · VCV3111812

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1422 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1422	likely benign
REVEL	0.577	indeterminate
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 8,233 bp · p 6.2e-16 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,060 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00167% 27/1,613,910 alleles · ultra-rare exomes 23/1,461,856 · genomes 4/152,054 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
Admixed American	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.000763%	131,107

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: ITPR3
Protein: p.Asp2428Val
Coding: c.7283A>T
MANE Select: NM_002224
dbSNP: rs531503671
Type: single nucleotide variant
Location: chr6:33691672 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.04 · 24 PDB

Full ITPR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ITPR3 p.Thr1424Met Pathogenic/Likely pathogenic ★★ ⚠ same type
ITPR3 p.Ala1352Thr Uncertain significance ★★ ⚠ same type
ITPR3 p.Arg1085Leu Uncertain significance ★★ ⚠ same type
ITPR3 p.Arg2659Cys Uncertain significance ★★ ⚠ same type
ITPR3 p.Asp1968Val Uncertain significance ★★ ⚠ same type
ITPR3 p.Glu669Asp Uncertain significance ★★ ⚠ same type
ITPR3 p.Gly1008Trp Uncertain significance ★★ ⚠ same type
ITPR3 p.Gly2514Glu Uncertain significance ★★ ⚠ 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/itpr3-p-asp2428val (accessed [today's date]).

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