Is ITPR1 p.Asn47= (c.141C>T) pathogenic?

ITPR1 p.Asn47= (c.141C>T) is classified Benign/Likely benign in ITPR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.0801%, afr); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Asn47= (c.141C>T)?

ITPR1 p.Asn47= (c.141C>T) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Asn47= (c.141C>T) in the general population?

ITPR1 p.Asn47= (c.141C>T) is ultra-rare (popmax 0.0801%, afr) (gnomAD).

ITPR1 p.Asn47=

c.141C>T · rs370939479 · VCV586039

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0801%, afr)

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 0.82	GERP -0.001, phastCons 1
Overall
CADD	8.701	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0801% African / African-American · 60/74,928 alleles

Filtering AF 0.0638% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.00446% 72/1,613,408 alleles · ultra-rare exomes 30/1,461,194 · genomes 42/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0801%	1,249
Admixed American	0.00333%	29,999
Remaining individualsnot grpmax-eligible	0.0032%	31,220
European (non-Finnish)	0.000678%	147,436

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.Asn47=
Coding: c.141C>T
MANE Select: NM_001378452
dbSNP: rs370939479
Type: single nucleotide variant
Location: chr3:4521072 (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.Asn47Lys Uncertain significance ★ same residue
ITPR1 p.Asn47Ser Conflicting classifications of pathogenicity ★ 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-asn47 (accessed [today's date]).

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