Is ITPR1 p.Thr83Ser (c.248C>G) pathogenic?

ITPR1 p.Thr83Ser (c.248C>G) is classified Uncertain significance in ITPR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-22). AlphaMissense: likely benign (0.1082); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with ITPR1 p.Thr83Ser (c.248C>G)?

ITPR1 p.Thr83Ser (c.248C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ITPR1 p.Thr83Ser (c.248C>G) in the general population?

ITPR1 p.Thr83Ser (c.248C>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ITPR1 p.Thr83Ser (c.248C>G)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

ITPR1 p.Thr83Ser

c.248C>G · rs774483090 · VCV2237277

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.417	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.34, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 129 kb · p 1.8e-14 · regional, not allelic
Overall
CADD	21.6	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 0.00333% Admixed American · 2/59,998 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,613,490 alleles · very rare exomes 3/1,461,216 · genomes 0/152,274 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,999
European (non-Finnish)	8.48e-05%	1,179,567

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: ITPR1
Protein: p.Thr83Ser
Coding: c.248C>G
MANE Select: NM_001378452
dbSNP: rs774483090
Type: single nucleotide variant
Location: chr3:4627847 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)

Full ITPR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITPR1 p.Leu605Phe Likely pathogenic ★★ same condition
ITPR1 p.Thr2434Ile Likely pathogenic ★★ same condition
ITPR1 c.1554+4G>A Uncertain significance ★★ same condition
ITPR1 c.3564+5G>T Uncertain significance ★★ same condition
ITPR1 p.Ala1222Thr Uncertain significance ★★ ⚠ same condition
ITPR1 p.Ala1222Val Uncertain significance ★★ same condition
ITPR1 p.Ala1480Thr Uncertain significance ★★ same condition
ITPR1 p.Ala1743Val 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/itpr1-p-thr83ser (accessed [today's date]).

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