Is TSC1 p.Ser511fs (c.1531dup) pathogenic?

TSC1 p.Ser511fs (c.1531dup) is classified Pathogenic in TSC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-18). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with TSC1 p.Ser511fs (c.1531dup)?

TSC1 p.Ser511fs (c.1531dup) is associated with hereditary neoplastic syndrome (ClinVar).

How common is TSC1 p.Ser511fs (c.1531dup) in the general population?

TSC1 p.Ser511fs (c.1531dup) is no gnomAD frequency available for this variant (gnomAD).

TSC1 p.Ser511fs

c.1531dup · rs1845652182 · VCV974575

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 15 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TSC1
Protein: p.Ser511fs
Coding: c.1531dup
MANE Select: NM_000368
dbSNP: rs1845652182
Type: Duplication
Location: chr9:132906046 (GRCh38)
Gene constraint: LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.55 · 5 PDB
Residue 511: the 'mediates interaction with wdr45b' region; a modified residue (phosphoserine); 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.Ser511= Benign/Likely benign ★★ same residue
TSC1 p.Arg420fs Pathogenic ★★ same condition
TSC1 p.Leu213fs Pathogenic ★★ same condition
TSC1 p.Tyr176fs Pathogenic ★★ same condition
TSC1 c.2624_2625+3dup Uncertain significance ★★ same condition
TSC1 p.Gly1037dup Uncertain significance ★★ same condition
TSC1 p.Leu369_Ser370insLeu Uncertain significance ★★ same condition
TSC1 c.107-7_107-3dup Likely benign ★★ 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-ser511fs (accessed [today's date]).

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