Is TUSC3 p.Arg82= (c.246A>C) pathogenic?

TUSC3 p.Arg82= (c.246A>C) is classified Likely benign in TUSC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). Very rare (popmax 0.00167%, amr); Associated with intellectual disability, autosomal recessive 7.

What condition is associated with TUSC3 p.Arg82= (c.246A>C)?

TUSC3 p.Arg82= (c.246A>C) is associated with intellectual disability, autosomal recessive 7 (ClinVar).

How common is TUSC3 p.Arg82= (c.246A>C) in the general population?

TUSC3 p.Arg82= (c.246A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

TUSC3 p.Arg82=

c.246A>C · VCV3684596

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

intellectual disability, autosomal recessive 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP -1.5, phastCons 0.76
Overall
CADD	7.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,998 alleles

Overall 6.2e-05% 1/1,613,674 alleles · very rare exomes 0/1,461,380 · genomes 1/152,294 · 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: TUSC3
Protein: p.Arg82=
Coding: c.246A>C
MANE Select: NM_006765
Type: single nucleotide variant
Location: chr8:15623187 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.78 · 4 PDB
Residue 82: the thioredoxin domain

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

Disease context

intellectual disability, autosomal recessive 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TUSC3 p.Arg82Gly Uncertain significance ★ ⚠ same residue
TUSC3 p.Arg82Ter Pathogenic ★ same residue
TUSC3 p.Arg74Ter Likely pathogenic ★★ same condition
TUSC3 p.Gln177Ter Pathogenic ★★ same condition
TUSC3 p.Ser331Ter Pathogenic/Likely pathogenic ★★ same condition
TUSC3 p.Ala13Val Uncertain significance ★★ ⚠ same condition
TUSC3 p.Arg15Gln Uncertain significance ★★ ⚠ same condition
TUSC3 p.Arg15Pro 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-arg82 (accessed [today's date]).

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