Is ITPR1 p.Ala19= (c.57G>A) pathogenic?

ITPR1 p.Ala19= (c.57G>A) is classified Benign in ITPR1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-25). Common (popmax 5.46%, sas) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Ala19= (c.57G>A)?

ITPR1 p.Ala19= (c.57G>A) is associated with autosomal dominant cerebellar ataxia, spinocerebellar ataxia type 29, aniridia-cerebellar ataxia-intellectual disability syndrome (ClinVar).

ITPR1 p.Ala19=

Q: How common is ITPR1 p.Ala19= (c.57G>A) in the general population?

ITPR1 p.Ala19= (c.57G>A) is common (popmax 5.46%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.57G>A · rs200534989 · VCV345338

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 5.46%, sas) — too common for a highly-penetrant pathogenic allele

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 -2.3	GERP -3.4
Overall
CADD	7.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.46% South Asian · 4,829/88,474 alleles

Filtering AF 5.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.28%

Overall 0.328% 5,255/1,604,280 alleles · common exomes 4,930/1,452,020 · genomes 325/152,260 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	5.46%	18
Middle Eastern	0.462%	216
Remaining individualsnot grpmax-eligible	0.389%	257
African / African-American	0.047%	2,130
European (non-Finnish)	0.00987%	10,137
Admixed American	0.00684%	14,626
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,480

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.Ala19=
Coding: c.57G>A
MANE Select: NM_001378452
dbSNP: rs200534989
Type: single nucleotide variant
Location: chr3:4516548 (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

Also linked: spinocerebellar ataxia type 29 aniridia-cerebellar ataxia-intellectual disability syndrome spinocerebellar ataxia type 15/16

Similar variants

ITPR1 p.Ala19Val Uncertain significance ★★ ⚠ same residue
ITPR1 p.Ala19Thr Uncertain significance ★ ⚠ same residue
ITPR1 p.Arg241Lys Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Arg269Trp Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Arg504Gly Likely pathogenic ★★ same condition
ITPR1 p.Arg506Trp Likely pathogenic ★★ same condition
ITPR1 p.Arg511Gly Likely pathogenic ★★ same condition
ITPR1 p.Arg511Ser Likely pathogenic ★★ 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-ala19 (accessed [today's date]).

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