Is ITPR2 p.Ala1007Val (c.3020C>T) pathogenic?

ITPR2 p.Ala1007Val (c.3020C>T) is classified Uncertain significance in ITPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.0635); Very rare (popmax 0.005%, amr).

How common is ITPR2 p.Ala1007Val (c.3020C>T) in the general population?

ITPR2 p.Ala1007Val (c.3020C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ITPR2 p.Ala1007Val (c.3020C>T)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

ITPR2 p.Ala1007Val

c.3020C>T · VCV4040421

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.93, phastCons 0.93
Regional constraint	o/e 0.91	unconstrained · MANE · 61 kb · p 0.0071 · regional, not allelic
Overall
CADD	7.154	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,954 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00397% 64/1,612,956 alleles · very rare exomes 59/1,460,722 · genomes 5/152,234 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,985
European (non-Finnish)	0.00483%	20,687
South Asian	0.0033%	30,332
Finnishnot grpmax-eligible	0.00156%	63,978

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.Ala1007Val
Coding: c.3020C>T
MANE Select: NM_002223
Type: single nucleotide variant
Location: chr12:26628077 (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-ala1007val (accessed [today's date]).

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