Is ITPR3 p.Phe1016= (c.3048C>T) pathogenic?

ITPR3 p.Phe1016= (c.3048C>T) is classified Likely benign in ITPR3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-01). Rare (popmax 0.677%, mid).

How common is ITPR3 p.Phe1016= (c.3048C>T) in the general population?

ITPR3 p.Phe1016= (c.3048C>T) is rare (popmax 0.677%, mid) (gnomAD).

ITPR3 p.Phe1016=

c.3048C>T · rs146528103 · VCV712371

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.677%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.6	GERP -0.2
Overall
CADD	10.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.677% Middle Eastern · 41/6,056 alleles

Filtering AF 0.513% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.455%

Overall 0.0622% 1,004/1,614,130 alleles · rare exomes 915/1,461,794 · genomes 89/152,336 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.78%	128
Middle Easterngrpmax	0.677%	148
Admixed American	0.132%	760
Remaining individualsnot grpmax-eligible	0.123%	812
South Asian	0.0527%	1,897
European (non-Finnish)	0.044%	2,274
East Asian	0.00891%	11,223
African / African-American	0.00666%	15,010

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ITPR3
Protein: p.Phe1016=
Coding: c.3048C>T
MANE Select: NM_002224
dbSNP: rs146528103
Type: single nucleotide variant
Location: chr6:33673710 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.04 · 24 PDB

Full ITPR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ITPR3 p.Thr1424Met Pathogenic/Likely pathogenic ★★ ⚠ same type
ITPR3 p.Ala1352Thr Uncertain significance ★★ ⚠ same type
ITPR3 p.Arg1085Leu Uncertain significance ★★ ⚠ same type
ITPR3 p.Arg2659Cys Uncertain significance ★★ ⚠ same type
ITPR3 p.Asp1968Val Uncertain significance ★★ ⚠ same type
ITPR3 p.Glu669Asp Uncertain significance ★★ ⚠ same type
ITPR3 p.Gly1008Trp Uncertain significance ★★ ⚠ same type
ITPR3 p.Gly2514Glu Uncertain significance ★★ ⚠ 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/itpr3-p-phe1016 (accessed [today's date]).

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