Is TSC2 p.Lys698= (c.2094G>A) pathogenic?

TSC2 p.Lys698= (c.2094G>A) is classified Likely benign in TSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). Very rare (popmax 0.00115%, sas); Associated with tuberous sclerosis 2.

What condition is associated with TSC2 p.Lys698= (c.2094G>A)?

TSC2 p.Lys698= (c.2094G>A) is associated with tuberous sclerosis 2 (ClinVar).

How common is TSC2 p.Lys698= (c.2094G>A) in the general population?

TSC2 p.Lys698= (c.2094G>A) is very rare (popmax 0.00115%, sas) (gnomAD).

How is Tuberous sclerosis complex inherited?

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

TSC2 p.Lys698=

c.2094G>A · VCV3729347

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00115%, sas)

Conditions

tuberous sclerosis 2

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 3.7	GERP -3.9, phastCons 1
Overall
CADD	6.942	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00115% South Asian · 1/87,090 alleles

Overall 0.00014% 2/1,426,590 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00115%	87,090
European (non-Finnish)	8.61e-05%	1,161,798

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.Lys698=
Coding: c.2094G>A
MANE Select: NM_000548
Type: single nucleotide variant
Location: chr16:2071931 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 698: an α-helix

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

Disease context

tuberous sclerosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Tuberous sclerosis complex (Orphanet):

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

Similar variants

TSC2 p.Lys698Asn Uncertain significance ★★ ⚠ same residue
TSC2 p.Lys698Glu Uncertain significance ★★ ⚠ same residue
TSC2 p.Lys698Met 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

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-lys698 (accessed [today's date]).

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