Is TUSC3 p.Arg63= (c.189C>G) pathogenic?

TUSC3 p.Arg63= (c.189C>G) is classified Uncertain significance in TUSC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with congenital disorder of glycosylation.

What condition is associated with TUSC3 p.Arg63= (c.189C>G)?

TUSC3 p.Arg63= (c.189C>G) is associated with congenital disorder of glycosylation (ClinVar).

How common is TUSC3 p.Arg63= (c.189C>G) in the general population?

TUSC3 p.Arg63= (c.189C>G) is absent from gnomAD v4.1 (gnomAD).

TUSC3 p.Arg63=

c.189C>G · rs751317981 · VCV908224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital disorder of glycosylation

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 -0.63	GERP 0.029, phastCons 0.017
Overall
CADD	7.797	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TUSC3
Protein: p.Arg63=
Coding: c.189C>G
MANE Select: NM_006765
dbSNP: rs751317981
Type: single nucleotide variant
Location: chr8:15623130 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.78 · 4 PDB
Residue 63: the thioredoxin domain

Full TUSC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TUSC3 p.Arg63Cys Uncertain significance ★ ⚠ same residue
TUSC3 p.Arg63Gly Uncertain significance ★ ⚠ same residue
TUSC3 p.Arg63Pro Uncertain significance ★ ⚠ same residue
TUSC3 c.*1197G>A Uncertain significance ★★ same condition
TUSC3 c.*1957A>G Uncertain significance ★★ same condition
TUSC3 p.Ala13Val Uncertain significance ★★ ⚠ same condition
TUSC3 p.Arg312Trp Uncertain significance ★★ ⚠ same condition
TUSC3 p.Arg9Gly 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/tusc3-p-arg63 (accessed [today's date]).

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