Is ITPR1 p.Lys669= (c.2007G>A) pathogenic?

ITPR1 p.Lys669= (c.2007G>A) is classified Benign in ITPR1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-03). Common (popmax 70.8%, amr) — too common for a highly-penetrant pathogenic allele; Associated with spinocerebellar ataxia type 15/16.

What condition is associated with ITPR1 p.Lys669= (c.2007G>A)?

ITPR1 p.Lys669= (c.2007G>A) is associated with spinocerebellar ataxia type 15/16, spinocerebellar ataxia type 29, aniridia-cerebellar ataxia-intellectual disability syndrome (ClinVar).

How is Spinocerebellar ataxia type 15/16 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ITPR1 p.Lys669=

Q: How common is ITPR1 p.Lys669= (c.2007G>A) in the general population?

ITPR1 p.Lys669= (c.2007G>A) is common (popmax 70.8%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2007G>A · rs2306875 · VCV129298

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 70.8%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

spinocerebellar ataxia type 15/16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.34	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.7	GERP 1.7, phastCons 1
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.8% Admixed American · 38,316/54,124 alleles

Filtering AF 70.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 70%

Overall 66.8% 1,049,285/1,569,864 alleles · common exomes 946,701/1,417,822 · genomes 102,584/152,042 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	70.8%	1
Amishnot grpmax-eligible	70.5%	1
Finnishnot grpmax-eligible	69.7%	1
African / African-American	69.3%	1
European (non-Finnish)	68.1%	1
Remaining individualsnot grpmax-eligible	65.1%	2
South Asian	64%	2
Middle Eastern	60.9%	2
Ashkenazi Jewishnot grpmax-eligible	60.2%	2
East Asian	34.8%	3

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.Lys669=
Coding: c.2007G>A
MANE Select: NM_001378452
dbSNP: rs2306875
Type: single nucleotide variant
Location: chr3:4670729 (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

spinocerebellar ataxia type 15/16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spinocerebellar ataxia type 29 aniridia-cerebellar ataxia-intellectual disability syndrome autosomal dominant cerebellar ataxia

For Spinocerebellar ataxia type 15/16 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

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
ITPR1 p.Gly2554Arg Pathogenic/Likely pathogenic ★★ same condition
ITPR1 p.Gly2595Glu 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-lys669 (accessed [today's date]).

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