Is ITPR1 p.Phe1291= (c.3873C>T) pathogenic?

ITPR1 p.Phe1291= (c.3873C>T) is classified Conflicting classifications of pathogenicity in ITPR1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2019-09-01). Very rare (popmax 0.00017%, nfe); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Phe1291= (c.3873C>T)?

ITPR1 p.Phe1291= (c.3873C>T) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Phe1291= (c.3873C>T) in the general population?

ITPR1 p.Phe1291= (c.3873C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

ITPR1 p.Phe1291=

c.3873C>T · rs567943387 · VCV752223

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

autosomal dominant cerebellar ataxia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.98, phastCons 1
Overall
CADD	12.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,326 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,012 alleles · very rare exomes 2/1,460,676 · genomes 0/152,336 · 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.Phe1291=
Coding: c.3873C>T
MANE Select: NM_001378452
dbSNP: rs567943387
Type: single nucleotide variant
Location: chr3:4691188 (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

Disease context

autosomal dominant cerebellar ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITPR1 p.Phe1291Leu Likely benign ★★ same residue
ITPR1 p.Phe1291Cys Uncertain significance ★ ⚠ same residue
ITPR1 c.*1531G>A Uncertain significance ★★ same condition
ITPR1 p.Arg1761Gln Uncertain significance ★★ same condition
ITPR1 p.Arg343Lys Uncertain significance ★★ same condition
ITPR1 p.Asp1959Asn Uncertain significance ★★ same condition
ITPR1 p.Glu2128Val Uncertain significance ★★ ⚠ same condition
ITPR1 p.Gly1782Arg 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-phe1291 (accessed [today's date]).

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