Is ITPR1 p.Ala146= (c.438C>T) pathogenic?

ITPR1 p.Ala146= (c.438C>T) is classified Benign in ITPR1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.7%, afr); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Ala146= (c.438C>T)?

ITPR1 p.Ala146= (c.438C>T) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Ala146= (c.438C>T) in the general population?

ITPR1 p.Ala146= (c.438C>T) is low-frequency (popmax 3.7%, afr) (gnomAD).

ITPR1 p.Ala146=

c.438C>T · rs61741506 · VCV345562

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.7%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP 2.2, phastCons 1
Overall
CADD	13.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.7% African / African-American · 2,765/74,676 alleles

Filtering AF 3.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.54%

Overall 0.199% 3,193/1,608,226 alleles · low-frequency exomes 1,604/1,455,998 · genomes 1,589/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.7%	27
Remaining individualsnot grpmax-eligible	0.262%	382
Admixed American	0.215%	465
Middle Eastern	0.149%	671
Ashkenazi Jewishnot grpmax-eligible	0.0204%	4,907
South Asian	0.0111%	9,007
European (non-Finnish)	0.00952%	10,508

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.Ala146=
Coding: c.438C>T
MANE Select: NM_001378452
dbSNP: rs61741506
Type: single nucleotide variant
Location: chr3:4642164 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 146: the mir 1 domain

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 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
ITPR1 p.Met2750Val Uncertain significance ★★ same condition
ITPR1 p.Ser2180Asn 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-ala146 (accessed [today's date]).

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