Is TSC2 p.Pro1763= (c.5289C>T) pathogenic?

TSC2 p.Pro1763= (c.5289C>T) is classified Benign/Likely benign in TSC2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-31). Ultra-rare (popmax 0.0534%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with TSC2 p.Pro1763= (c.5289C>T)?

TSC2 p.Pro1763= (c.5289C>T) is associated with hereditary neoplastic syndrome, tuberous sclerosis, polycystic kidney disease 1 (ClinVar).

How common is TSC2 p.Pro1763= (c.5289C>T) in the general population?

TSC2 p.Pro1763= (c.5289C>T) is ultra-rare (popmax 0.0534%, afr) (gnomAD).

TSC2 p.Pro1763=

c.5289C>T · rs144965811 · VCV413718

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0534%, afr)

Conditions

hereditary neoplastic syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.044	GERP -3.2, phastCons 0.77
Overall
CADD	5.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0534% African / African-American · 40/74,920 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0357%

Overall 0.00267% 43/1,612,818 alleles · ultra-rare exomes 19/1,460,610 · genomes 24/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0534%	1,873
Remaining individualsnot grpmax-eligible	0.0016%	62,472
European (non-Finnish)	0.000169%	590,019

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.Pro1763=
Coding: c.5289C>T
MANE Select: NM_000548
dbSNP: rs144965811
Type: single nucleotide variant
Location: chr16:2088475 (GRCh38)

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tuberous sclerosis polycystic kidney disease 1 tuberous sclerosis 2

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-pro1763 (accessed [today's date]).

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