Is ITPR2 p.Ala1983Val (c.5948C>T) pathogenic?

ITPR2 p.Ala1983Val (c.5948C>T) is classified Likely benign in ITPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-22). AlphaMissense: likely benign (0.0909); Very rare (popmax 0.000254%, nfe).

How common is ITPR2 p.Ala1983Val (c.5948C>T) in the general population?

ITPR2 p.Ala1983Val (c.5948C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ITPR2 p.Ala1983Val (c.5948C>T)?

AlphaMissense predicts likely benign (score 0.0909) — an in-silico prediction, not a clinical call.

ITPR2 p.Ala1983Val

c.5948C>T · rs1271921653 · VCV2405574

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
AlphaMissense	0.0909	likely benign
REVEL	0.379	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.85, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 169 kb · p 7.4e-06 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,960 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,076 alleles · very rare exomes 3/1,461,798 · genomes 0/152,278 · joint denominator

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.Ala1983Val
Coding: c.5948C>T
MANE Select: NM_002223
dbSNP: rs1271921653
Type: single nucleotide variant
Location: chr12:26483762 (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-ala1983val (accessed [today's date]).

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