Is ITPR1 p.Asp2191Val (c.6572A>T) pathogenic?

ITPR1 p.Asp2191Val (c.6572A>T) is classified Uncertain significance in ITPR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-18). AlphaMissense: likely pathogenic (0.7223); Very rare (popmax 0.00168%, amr).

How common is ITPR1 p.Asp2191Val (c.6572A>T) in the general population?

ITPR1 p.Asp2191Val (c.6572A>T) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about ITPR1 p.Asp2191Val (c.6572A>T)?

AlphaMissense predicts likely pathogenic (score 0.7223) — an in-silico prediction, not a clinical call.

ITPR1 p.Asp2191Val

c.6572A>T · rs1200988191 · VCV1929117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7223 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.7223	likely pathogenic
REVEL	0.814	moderately 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 2.8, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 12 kb · p 3.9e-10 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,614 alleles

Overall 6.21e-05% 1/1,610,576 alleles · very rare exomes 1/1,458,252 · genomes 0/152,324 · 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.Asp2191Val
Coding: c.6572A>T
MANE Select: NM_001378452
dbSNP: rs1200988191
Type: single nucleotide variant
Location: chr3:4783877 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)

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

Similar variants

ITPR1 p.Asp2191Gly Uncertain significance ★ ⚠ same residue
ITPR1 c.1252-1G>C Pathogenic/Likely pathogenic ★★ same type
ITPR1 c.1252-1G>T Pathogenic/Likely pathogenic ★★ same type
ITPR1 p.Arg241Lys Pathogenic/Likely pathogenic ★★ same type
ITPR1 p.Arg269Leu Pathogenic/Likely pathogenic ★★ same type
ITPR1 p.Arg269Trp Pathogenic/Likely pathogenic ★★ same type
ITPR1 p.Arg504Gly Likely pathogenic ★★ same type
ITPR1 p.Arg506Trp Likely pathogenic ★★ 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/itpr1-p-asp2191val (accessed [today's date]).

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