Is ITPR1 p.His244Pro (c.731A>C) pathogenic?

ITPR1 p.His244Pro (c.731A>C) is classified Likely pathogenic in ITPR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely pathogenic (0.9991); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ITPR1 p.His244Pro (c.731A>C)?

ITPR1 p.His244Pro (c.731A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ITPR1 p.His244Pro (c.731A>C) in the general population?

ITPR1 p.His244Pro (c.731A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITPR1 p.His244Pro (c.731A>C)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

ITPR1 p.His244Pro

c.731A>C · rs1085308010 · VCV522002

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic ✓ concordant with ClinVar · top 2% in ITPR1
REVEL	0.975	strongly pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 129 kb · p 1.8e-14 · regional, not allelic
Overall
CADD	27.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ITPR1
Protein: p.His244Pro
Coding: c.731A>C
MANE Select: NM_001378452
dbSNP: rs1085308010
Type: single nucleotide variant
Location: chr3:4645604 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 244: the mir 3 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITPR1 p.His244Arg Pathogenic/Likely pathogenic ★★ same residue
ITPR1 p.Leu605Phe Likely pathogenic ★★ same condition
ITPR1 p.Thr2434Ile Likely pathogenic ★★ same condition
ITPR1 c.1554+4G>A Uncertain significance ★★ same condition
ITPR1 c.3564+5G>T Uncertain significance ★★ same condition
ITPR1 p.Ala1222Thr Uncertain significance ★★ ⚠ same condition
ITPR1 p.Ala1222Val Uncertain significance ★★ same condition
ITPR1 p.Ala1480Thr Uncertain significance ★★ 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-his244pro (accessed [today's date]).

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