Is TSC1 p.Pro558Ser (c.1671_1672delinsTT) pathogenic?

TSC1 p.Pro558Ser (c.16711672delinsTT) is classified Uncertain significance in TSC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). No gnomAD frequency available for this variant; Associated with tuberous sclerosis 1.

What condition is associated with TSC1 p.Pro558Ser (c.1671_1672delinsTT)?

TSC1 p.Pro558Ser (c.1671_1672delinsTT) is associated with tuberous sclerosis 1 (ClinVar).

How common is TSC1 p.Pro558Ser (c.1671_1672delinsTT) in the general population?

TSC1 p.Pro558Ser (c.1671_1672delinsTT) is no gnomAD frequency available for this variant (gnomAD).

How is Tuberous sclerosis complex inherited?

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

TSC1 p.Pro558Ser

c.1671_1672delinsTT · rs2538728834 · VCV1716610

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

tuberous sclerosis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 4,448 bp · p 0.00013 · regional, not allelic

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.Pro558Ser
Coding: c.1671_1672delinsTT
MANE Select: NM_000368
dbSNP: rs2538728834
Type: Indel
Location: chr9:132905906 (GRCh38)
Gene constraint: LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.55 · 5 PDB
Residue 558: 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

tuberous sclerosis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Tuberous sclerosis complex (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Taiwan, Province of China)

Similar variants

TSC1 p.Pro558= Benign/Likely benign ★★ same residue
TSC1 p.Leu136fs Pathogenic/Likely pathogenic ★★ same condition
TSC1 p.Ala1026Phe Uncertain significance ★★ same condition
TSC1 p.Ala428Leu Uncertain significance ★★ same condition
TSC1 p.Gly1036Lys Uncertain significance ★★ same condition
TSC1 p.Gly38Asp Uncertain significance ★★ same condition
TSC1 p.Ile954Asn Uncertain significance ★★ same condition
TSC1 p.Leu1125_Gly1126delinsPheCys Uncertain significance ★★ 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-pro558ser (accessed [today's date]).

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