Is ITPR2 p.Ser635= (c.1905A>G) pathogenic?

ITPR2 p.Ser635= (c.1905A>G) is classified Benign in ITPR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-05). Common (popmax 36.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ITPR2-related disorder.

What condition is associated with ITPR2 p.Ser635= (c.1905A>G)?

ITPR2 p.Ser635= (c.1905A>G) is associated with ITPR2-related disorder (ClinVar).

ITPR2 p.Ser635=

Q: How common is ITPR2 p.Ser635= (c.1905A>G) in the general population?

ITPR2 p.Ser635= (c.1905A>G) is common (popmax 36.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1905A>G · rs12313993 · VCV3055783

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 36.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

ITPR2-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 -1.5	GERP -3.7
Overall
CADD	4.402	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.8% African / African-American · 26,921/73,062 alleles

Filtering AF 36.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.3%

Overall 17.5% 273,109/1,562,392 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	36.8%	3
Middle Eastern	28%	4
Amishnot grpmax-eligible	23.5%	4
South Asian	22.8%	4
Remaining individualsnot grpmax-eligible	18.5%	5
Finnishnot grpmax-eligible	18.3%	5
Ashkenazi Jewishnot grpmax-eligible	16.8%	6
European (non-Finnish)	16.6%	6
Admixed American	11.8%	8
East Asian	2.63%	38

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: ITPR2
Protein: p.Ser635=
Coding: c.1905A>G
MANE Select: NM_002223
dbSNP: rs12313993
Type: single nucleotide variant
Location: chr12:26658112 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)

Full ITPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ITPR2-related disorder

Similar variants

ITPR2 c.279+6G>C Benign same condition
ITPR2 c.3122+4T>C Likely benign same condition
ITPR2 c.3552+3C>T Likely benign same condition
ITPR2 c.4381-8C>T Likely benign same condition
ITPR2 p.Ala2112= Likely benign same condition
ITPR2 p.Ala898= Benign same condition
ITPR2 p.Asp2103= Likely benign same condition
ITPR2 p.Glu815= Likely benign 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/itpr2-p-ser635 (accessed [today's date]).

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