Is TSC2 p.Pro237= (c.711G>A) pathogenic?

TSC2 p.Pro237= (c.711G>A) is classified Benign/Likely benign in TSC2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-09-21). Ultra-rare (popmax 0.0165%, mid); Associated with tuberous sclerosis.

What condition is associated with TSC2 p.Pro237= (c.711G>A)?

TSC2 p.Pro237= (c.711G>A) is associated with tuberous sclerosis, tuberous sclerosis 2, hereditary neoplastic syndrome (ClinVar).

How common is TSC2 p.Pro237= (c.711G>A) in the general population?

TSC2 p.Pro237= (c.711G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Tuberous sclerosis complex inherited?

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

TSC2 p.Pro237=

c.711G>A · rs189380607 · VCV468177

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

tuberous sclerosis

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 -8.2	GERP -3.7
Overall
CADD	0.487	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00186% 30/1,612,462 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
South Asian	0.00769%	13,012
East Asian	0.00223%	44,878
European (non-Finnish)	0.00169%	59,000
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Pro237=
Coding: c.711G>A
MANE Select: NM_000548
dbSNP: rs189380607
Type: single nucleotide variant
Location: chr16:2056706 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 237: an α-helix; the 'required for interaction with tsc1' region

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

Disease context

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

Also linked: tuberous sclerosis 2 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.Pro237Ala Uncertain significance ★★ ⚠ same residue
TSC2 p.Pro237Arg Uncertain significance ★★ ⚠ same residue
TSC2 p.Pro237Ser Uncertain significance ★★ ⚠ same residue
TSC2 p.Pro237Gln Uncertain significance ★ ⚠ same residue
TSC2 p.Pro237Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC2 p.Pro237fs Likely pathogenic 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-pro237 (accessed [today's date]).

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