Is TSC2 p.Pro1156= (c.3468A>G) pathogenic?

TSC2 p.Pro1156= (c.3468A>G) is classified Benign/Likely benign in TSC2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0413%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with TSC2 p.Pro1156= (c.3468A>G)?

TSC2 p.Pro1156= (c.3468A>G) is associated with hereditary neoplastic syndrome, tuberous sclerosis, tuberous sclerosis 2 (ClinVar).

How common is TSC2 p.Pro1156= (c.3468A>G) in the general population?

TSC2 p.Pro1156= (c.3468A>G) is ultra-rare (popmax 0.0413%, afr) (gnomAD).

TSC2 p.Pro1156=

c.3468A>G · rs147242130 · VCV380698

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, afr)

Conditions

hereditary neoplastic syndrome

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 -7.1	GERP -3.5
Overall
CADD	0.065	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0413% African / African-American · 31/75,070 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00248% 40/1,612,992 alleles · ultra-rare exomes 25/1,460,610 · genomes 15/152,382 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0413%	2,422
Middle Eastern	0.0165%	6,062
Admixed American	0.005%	20,009
Remaining individualsnot grpmax-eligible	0.0048%	20,831
European (non-Finnish)	0.000169%	590,012

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.Pro1156=
Coding: c.3468A>G
MANE Select: NM_000548
dbSNP: rs147242130
Type: single nucleotide variant
Location: chr16:2080235 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 1156: the 'disordered' region

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 tuberous sclerosis 2

Similar variants

TSC2 p.Pro1156Ser Uncertain significance ★★ ⚠ same residue
TSC2 p.Pro1156Leu 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-pro1156 (accessed [today's date]).

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