Is TUSC3 p.Ser281= (c.843A>G) pathogenic?

TUSC3 p.Ser281= (c.843A>G) is classified Uncertain significance in TUSC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0107%, afr); Associated with congenital disorder of glycosylation.

What condition is associated with TUSC3 p.Ser281= (c.843A>G)?

TUSC3 p.Ser281= (c.843A>G) is associated with congenital disorder of glycosylation (ClinVar).

How common is TUSC3 p.Ser281= (c.843A>G) in the general population?

TUSC3 p.Ser281= (c.843A>G) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

TUSC3 p.Ser281=

c.843A>G · rs202151515 · VCV910175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

congenital disorder of glycosylation

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 -1.1	GERP -3.7
Overall
CADD	9.952	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/75,010 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000496% 8/1,613,226 alleles · ultra-rare exomes 6/1,460,976 · genomes 2/152,250 · 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.Ser281=
Coding: c.843A>G
MANE Select: NM_006765
dbSNP: rs202151515
Type: single nucleotide variant
Location: chr8:15730710 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.78 · 4 PDB

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 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
TUSC3 p.Ser8Leu Uncertain significance ★★ ⚠ same condition
TUSC3 c.309-6T>C Benign ★★ same condition
TUSC3 c.-108G>A Likely benign ★★ 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-ser281 (accessed [today's date]).

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