Is TSC2 p.Pro1766= (c.5298T>A) pathogenic?

TSC2 p.Pro1766= (c.5298T>A) is classified Likely benign in TSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). Absent from gnomAD v4.1; Associated with tuberous sclerosis 2.

What condition is associated with TSC2 p.Pro1766= (c.5298T>A)?

TSC2 p.Pro1766= (c.5298T>A) is associated with tuberous sclerosis 2 (ClinVar).

How common is TSC2 p.Pro1766= (c.5298T>A) in the general population?

TSC2 p.Pro1766= (c.5298T>A) is absent from gnomAD v4.1 (gnomAD).

How is Tuberous sclerosis complex inherited?

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

TSC2 p.Pro1766=

c.5298T>A · rs2151638999 · VCV1151320

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

tuberous sclerosis 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.95	GERP -3.2, phastCons 0.001
Overall
CADD	0.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TSC2
Protein: p.Pro1766=
Coding: c.5298T>A
MANE Select: NM_000548
dbSNP: rs2151638999
Type: single nucleotide variant
Location: chr16:2088484 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 1766: the 'disordered' region

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.Pro1766Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC2 p.Pro1766Ser Conflicting classifications of pathogenicity ★ ⚠ 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-pro1766 (accessed [today's date]).

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