Is ITPR1 p.Asp231Val (c.692A>T) pathogenic?

ITPR1 p.Asp231Val (c.692A>T) is classified Uncertain significance in ITPR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-21). AlphaMissense: likely benign (0.3125); Very rare (popmax 0.000424%, nfe); Associated with ITPR1-related disorder.

What condition is associated with ITPR1 p.Asp231Val (c.692A>T)?

ITPR1 p.Asp231Val (c.692A>T) is associated with ITPR1-related disorder, aniridia-cerebellar ataxia-intellectual disability syndrome (ClinVar).

How common is ITPR1 p.Asp231Val (c.692A>T) in the general population?

ITPR1 p.Asp231Val (c.692A>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ITPR1 p.Asp231Val (c.692A>T)?

AlphaMissense predicts likely benign (score 0.3125) — an in-silico prediction, not a clinical call.

ITPR1 p.Asp231Val

c.692A>T · rs1389658278 · VCV2582314

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ITPR1-related disorder

Computational evidence

Protein change
AlphaMissense	0.3125	likely benign
REVEL	0.736	pathogenic-leaning
SaProt	LLR -6.99	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 129 kb · p 1.8e-14 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,122 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,612,916 alleles · very rare exomes 4/1,460,794 · genomes 1/152,122 · joint denominator

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: ITPR1
Protein: p.Asp231Val
Coding: c.692A>T
MANE Select: NM_001378452
dbSNP: rs1389658278
Type: single nucleotide variant
Location: chr3:4645454 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 231: the mir 3 domain

Full ITPR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ITPR1-related disorder

Also linked: aniridia-cerebellar ataxia-intellectual disability syndrome

Similar variants

ITPR1 p.Asp231= Likely benign ★★ same residue
ITPR1 c.1252-1G>C Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Arg269Trp Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Arg506Trp Likely pathogenic ★★ same condition
ITPR1 p.Glu2109Lys Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Gly2554Arg Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Ile2598Thr Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Tyr567Cys Pathogenic ★★ same condition

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/itpr1-p-asp231val (accessed [today's date]).

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