Is ITPR3 p.His1852= (c.5556C>T) pathogenic?

ITPR3 p.His1852= (c.5556C>T) is classified Likely benign in ITPR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-05). Rare (popmax 0.129%, sas); Associated with ITPR3-related disorder.

What condition is associated with ITPR3 p.His1852= (c.5556C>T)?

ITPR3 p.His1852= (c.5556C>T) is associated with ITPR3-related disorder (ClinVar).

How common is ITPR3 p.His1852= (c.5556C>T) in the general population?

ITPR3 p.His1852= (c.5556C>T) is rare (popmax 0.129%, sas) (gnomAD).

ITPR3 p.His1852=

c.5556C>T · rs373226771 · VCV3046564

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.129%, sas)

Conditions

ITPR3-related disorder

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 -8.1	GERP -4.2
Overall
CADD	1.767	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% South Asian · 117/90,678 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.0141% 227/1,608,258 alleles · rare exomes 204/1,455,898 · genomes 23/152,360 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.129%	775
Remaining individualsnot grpmax-eligible	0.0482%	2,074
East Asian	0.0469%	2,130
Middle Eastern	0.0165%	6,044
European (non-Finnish)	0.00442%	22,620
African / African-American	0.004%	24,986
Admixed American	0.00335%	29,864
Finnishnot grpmax-eligible	0.00158%	63,306

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: ITPR3
Protein: p.His1852=
Coding: c.5556C>T
MANE Select: NM_002224
dbSNP: rs373226771
Type: single nucleotide variant
Location: chr6:33685716 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.04 · 24 PDB

Full ITPR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ITPR3-related disorder

Similar variants

ITPR3 p.His1852Tyr Uncertain significance ★ ⚠ same residue
ITPR3 p.Arg2524Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
ITPR3 c.283-9T>A Uncertain significance same condition
ITPR3 p.Ala1530Pro Uncertain significance ⚠ same condition
ITPR3 p.Gly1812Ser Uncertain significance ⚠ same condition
ITPR3 p.Gly919Cys Uncertain significance ⚠ same condition
ITPR3 p.Ile1969Met Uncertain significance ⚠ same condition
ITPR3 p.Ser120Arg 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/itpr3-p-his1852 (accessed [today's date]).

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