Is TSC1 p.Phe552fs (c.1654_1655delinsCCTTGTTGTT…[142 bp]) pathogenic?

TSC1 p.Phe552fs (c.16541655delinsCCTTGTTGTT…[142 bp]) is classified Pathogenic in TSC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-11). Absent from gnomAD; Associated with tuberous sclerosis 1.

What condition is associated with TSC1 p.Phe552fs (c.1654_1655delinsCCTTGTTGTT…[142 bp])?

TSC1 p.Phe552fs (c.1654_1655delinsCCTTGTTGTT…[142 bp]) is associated with tuberous sclerosis 1 (ClinVar).

How common is TSC1 p.Phe552fs (c.1654_1655delinsCCTTGTTGTT…[142 bp]) in the general population?

TSC1 p.Phe552fs (c.1654_1655delinsCCTTGTTGTT…[142 bp]) is absent from gnomAD (gnomAD).

How is Tuberous sclerosis complex inherited?

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

TSC1 p.Phe552fs

c.1654_1655delinsCCTTGTTGTT…[142 bp] · rs2538730433 · VCV2030066

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

tuberous sclerosis 1

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 11	GERP 2.1, 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.Phe552fs
Coding: c.1654_1655delinsCCTTGTTGTTGGCCTTCTTCAGTTCTATCCGCAGCTCCGCAATCATGTTCCTGCAGTCCTCCAGCTTCGTCTGCCCAAAGAGACGTGGACATGAAGTTTGAGGAACACCAACAGGCCAGATCACAGGCCTACCTACAAAGTC
MANE Select: NM_000368
dbSNP: rs2538730433
Type: Indel
Location: chr9:132905923 (GRCh38)
Gene constraint: LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.55 · 5 PDB
Residue 552: 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.Phe552= 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-phe552fs (accessed [today's date]).

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