Is TSC2 p.Pro669= (c.2007T>C) pathogenic?

TSC2 p.Pro669= (c.2007T>C) is classified Likely benign in TSC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-20). No allele count reported in gnomAD v4.1 (AN 1,576,720); Associated with tuberous sclerosis 2.

What condition is associated with TSC2 p.Pro669= (c.2007T>C)?

TSC2 p.Pro669= (c.2007T>C) is associated with tuberous sclerosis 2, hereditary neoplastic syndrome (ClinVar).

How common is TSC2 p.Pro669= (c.2007T>C) in the general population?

TSC2 p.Pro669= (c.2007T>C) is no allele count reported in gnomAD v4.1 (AN 1,576,720) (gnomAD).

How is Tuberous sclerosis complex inherited?

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

TSC2 p.Pro669=

c.2007T>C · rs2151305733 · VCV1604467

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,576,720)

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 -6.4	GERP -3.1
Overall
CADD	0.055	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,576,720). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TSC2
Protein: p.Pro669=
Coding: c.2007T>C
MANE Select: NM_000548
dbSNP: rs2151305733
Type: single nucleotide variant
Location: chr16:2071844 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 669: 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

Also linked: 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.Pro669Leu Uncertain significance ★★ ⚠ same residue
TSC2 p.Pro669Ser Uncertain significance ★★ ⚠ same residue
TSC2 p.Pro669Thr Uncertain significance ★★ ⚠ same residue
TSC2 p.Pro669Ala Uncertain significance ★ ⚠ same residue
TSC2 p.Pro669Arg Uncertain significance ★ ⚠ same residue
TSC2 p.Pro669His Uncertain significance ★ ⚠ same residue
TSC2 c.1257+1G>A Pathogenic ★★ same condition
TSC2 c.1258-2A>G 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-pro669 (accessed [today's date]).

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