Is ITPR1 p.Ser1618= (c.4854C>T) pathogenic?

ITPR1 p.Ser1618= (c.4854C>T) is classified Benign/Likely benign in ITPR1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-11-28). Low-frequency (popmax 1.08%, mid); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with ITPR1 p.Ser1618= (c.4854C>T)?

ITPR1 p.Ser1618= (c.4854C>T) is associated with autosomal dominant cerebellar ataxia (ClinVar).

How common is ITPR1 p.Ser1618= (c.4854C>T) in the general population?

ITPR1 p.Ser1618= (c.4854C>T) is low-frequency (popmax 1.08%, mid) (gnomAD).

ITPR1 p.Ser1618=

c.4854C>T · rs373127487 · VCV345741

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, mid)

Conditions

autosomal dominant cerebellar ataxia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -9.3	GERP -4.3
Overall
CADD	1.885	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.08% Middle Eastern · 61/5,628 alleles

Filtering AF 0.866% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.787%

Overall 0.0422% 658/1,560,426 alleles · low-frequency exomes 604/1,408,152 · genomes 54/152,274 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.08%	92
Admixed American	0.0955%	1,047
Remaining individualsnot grpmax-eligible	0.0696%	1,437
European (non-Finnish)	0.0411%	2,434
African / African-American	0.0257%	3,889
South Asian	0.00826%	12,110
East Asian	0.00706%	14,155
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,632
Finnishnot grpmax-eligible	0.00326%	30,640

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.Ser1618=
Coding: c.4854C>T
MANE Select: NM_001378452
dbSNP: rs373127487
Type: single nucleotide variant
Location: chr3:4710336 (GRCh38)

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

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-ser1618 (accessed [today's date]).

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