Is ITPR2 p.Asn24Ser (c.71A>G) pathogenic?

ITPR2 p.Asn24Ser (c.71A>G) is classified Likely benign in ITPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0697); Low-frequency (popmax 1%, afr).

How common is ITPR2 p.Asn24Ser (c.71A>G) in the general population?

ITPR2 p.Asn24Ser (c.71A>G) is low-frequency (popmax 1%, afr) (gnomAD).

What do computational predictors say about ITPR2 p.Asn24Ser (c.71A>G)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

ITPR2 p.Asn24Ser

c.71A>G · rs2230371 · VCV786604

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.327	indeterminate
SaProt	LLR -4.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 175 kb · p 1.6e-22 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1% African / African-American · 730/72,860 alleles

Filtering AF 0.942% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.918%

Overall 0.0521% 834/1,600,328 alleles · low-frequency exomes 401/1,448,036 · genomes 433/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1%	100
Remaining individualsnot grpmax-eligible	0.0888%	1,127
Admixed American	0.0409%	2,443
Middle Eastern	0.0166%	6,018
European (non-Finnish)	0.00196%	51,055
South Asian	0.00112%	89,448

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.Asn24Ser
Coding: c.71A>G
MANE Select: NM_002223
dbSNP: rs2230371
Type: single nucleotide variant
Location: chr12:26832711 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)

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

Similar variants

ITPR2 p.Val1162Gly Uncertain significance ★★ same type
ITPR2 c.3801+23G>A Benign ★★ same type
ITPR2 c.5073+10T>A Benign ★★ same type
ITPR2 c.93-10T>A Benign ★★ same type
ITPR2 p.Ala1898Val Benign ★★ same type
ITPR2 p.Arg1180Gln Likely benign ★★ same type
ITPR2 p.Arg1275Gln Likely benign ★★ same type
ITPR2 p.Asn461= Benign ★★ same type

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-asn24ser (accessed [today's date]).

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