Is TSC2 p.Arg936= (c.2808G>C) pathogenic?

TSC2 p.Arg936= (c.2808G>C) is classified Benign/Likely benign in TSC2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-05-27). Ultra-rare (popmax 0.012%, afr); Associated with tuberous sclerosis.

What condition is associated with TSC2 p.Arg936= (c.2808G>C)?

TSC2 p.Arg936= (c.2808G>C) is associated with tuberous sclerosis, tuberous sclerosis 2, hereditary neoplastic syndrome (ClinVar).

How common is TSC2 p.Arg936= (c.2808G>C) in the general population?

TSC2 p.Arg936= (c.2808G>C) is ultra-rare (popmax 0.012%, afr) (gnomAD).

How is Tuberous sclerosis complex inherited?

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

TSC2 p.Arg936=

c.2808G>C · rs147003028 · VCV1923125

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Conditions

tuberous sclerosis

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 2.4	GERP -0.79, phastCons 1
Overall
CADD	7.411	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/75,024 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00062% 10/1,613,478 alleles · ultra-rare exomes 7/1,461,234 · genomes 3/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,336
East Asian	0.00223%	44,868

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.Arg936=
Coding: c.2808G>C
MANE Select: NM_000548
dbSNP: rs147003028
Type: single nucleotide variant
Location: chr16:2076556 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 936: an α-helix; the 'disordered' 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.Arg936Gln Uncertain significance ★★ ⚠ same residue
TSC2 p.Arg936Trp Uncertain significance ★★ ⚠ same residue
TSC2 p.Arg936Gly Uncertain significance ★ ⚠ same residue
TSC2 p.Arg936fs Pathogenic ★ 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

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-arg936 (accessed [today's date]).

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