Is TSC1 p.Pro169= (c.507A>G) pathogenic?

TSC1 p.Pro169= (c.507A>G) is classified Uncertain significance in TSC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-03). Absent from gnomAD v4.1; Associated with isolated focal cortical dysplasia type II.

What condition is associated with TSC1 p.Pro169= (c.507A>G)?

TSC1 p.Pro169= (c.507A>G) is associated with isolated focal cortical dysplasia type II, tuberous sclerosis 1 (ClinVar).

How common is TSC1 p.Pro169= (c.507A>G) in the general population?

TSC1 p.Pro169= (c.507A>G) is absent from gnomAD v4.1 (gnomAD).

TSC1 p.Pro169=

c.507A>G · rs1846669296 · VCV963841

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

isolated focal cortical dysplasia type II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.87	donor gain · deltas
Pangolin	Δ0.75	gain · loss 0.46 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.2	GERP 1.5, phastCons 1
Overall
CADD	25.7	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: TSC1
Protein: p.Pro169=
Coding: c.507A>G
MANE Select: NM_000368
dbSNP: rs1846669296
Type: single nucleotide variant
Location: chr9:132923349 (GRCh38)
Gene constraint: LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.55 · 5 PDB
Residue 169: a UniProt-annotated variant site (in tsc1)

Full TSC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

isolated focal cortical dysplasia type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tuberous sclerosis 1

For Isolated focal cortical dysplasia (Orphanet):

Onset: All ages

Similar variants

TSC1 p.Pro169Arg Uncertain significance ★★ ⚠ same residue
TSC1 p.Pro169Ser Uncertain significance ★★ ⚠ same residue
TSC1 p.Pro169Gln Uncertain significance ★ ⚠ same residue
TSC1 c.1029+1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.1029+1G>C Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.107-1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.1141+1G>A Likely pathogenic ★★ same condition
TSC1 c.1264-1G>A Pathogenic/Likely 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/tsc1-p-pro169 (accessed [today's date]).

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