Is TSC2 p.Arg293= (c.879A>G) pathogenic?

TSC2 p.Arg293= (c.879A>G) is classified Conflicting classifications of pathogenicity in TSC2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-23). Very rare (popmax 0.00419%, nfe); Associated with tuberous sclerosis.

What condition is associated with TSC2 p.Arg293= (c.879A>G)?

TSC2 p.Arg293= (c.879A>G) is associated with tuberous sclerosis, tuberous sclerosis 2, hereditary neoplastic syndrome (ClinVar).

How common is TSC2 p.Arg293= (c.879A>G) in the general population?

TSC2 p.Arg293= (c.879A>G) is very rare (popmax 0.00419%, nfe) (gnomAD).

How is Tuberous sclerosis complex inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TSC2 p.Arg293=

c.879A>G · rs369222477 · VCV701704

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00419%, nfe)

Conditions

tuberous sclerosis

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 2.1	GERP -0.62, phastCons 1
Overall
CADD	7.933	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00419% European (non-Finnish) · 49/1,168,578 alleles

Filtering AF 0.00321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00289%

Overall 0.00361% 52/1,439,062 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00419%	23,849
Remaining individualsnot grpmax-eligible	0.00324%	30,843
African / African-American	0.00134%	74,896

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: TSC2
Protein: p.Arg293=
Coding: c.879A>G
MANE Select: NM_000548
dbSNP: rs369222477
Type: single nucleotide variant
Location: chr16:2058777 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 293: an α-helix; the 'required for interaction with tsc1' region

Full TSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tuberous sclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tuberous sclerosis 2 hereditary neoplastic syndrome

For Tuberous sclerosis complex (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Taiwan, Province of China)

Similar variants

TSC2 p.Arg293Lys Uncertain significance ★ ⚠ same residue
TSC2 p.Arg293Ser Uncertain significance ★ ⚠ same residue
TSC2 c.1257+1G>A Pathogenic ★★ same condition
TSC2 c.1258-2A>G Pathogenic ★★ same condition
TSC2 c.1361+1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.1361+1G>T Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.1362-1G>A Pathogenic ★★ same condition
TSC2 c.138+2T>C Pathogenic ★★ 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/tsc2-p-arg293 (accessed [today's date]).

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