Is TSC1 p.Asp504= (c.1512C>T) pathogenic?

TSC1 p.Asp504= (c.1512C>T) is classified Likely benign in TSC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with TSC1 p.Asp504= (c.1512C>T)?

TSC1 p.Asp504= (c.1512C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is TSC1 p.Asp504= (c.1512C>T) in the general population?

TSC1 p.Asp504= (c.1512C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

TSC1 p.Asp504=

c.1512C>T · rs2131845912 · VCV2560382

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.2	GERP -0.51, phastCons 1
Overall
CADD	9.271	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,006 alleles

Overall 6.2e-05% 1/1,614,084 alleles · very rare exomes 1/1,461,790 · genomes 0/152,294 · joint denominator

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: TSC1
Protein: p.Asp504=
Coding: c.1512C>T
MANE Select: NM_000368
dbSNP: rs2131845912
Type: single nucleotide variant
Location: chr9:132906066 (GRCh38)
Gene constraint: LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.55 · 5 PDB
Residue 504: the 'mediates interaction with wdr45b' region; the 'disordered' region; a UniProt-annotated variant site (in tsc1)

Full TSC1 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

Similar variants

TSC1 p.Asp504Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC1 c.1029+1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.1997+2T>G Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.1998-1G>T Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.2042-5A>G Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.2208+2T>A Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.2626-2A>C Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.664-15A>G 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-asp504 (accessed [today's date]).

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