Is TSC2 p.Phe1806fs (c.5417_5418del) pathogenic?

TSC2 p.Phe1806fs (c.54175418del) is classified Conflicting classifications of pathogenicity in TSC2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-22). No gnomAD frequency available for this variant; Associated with tuberous sclerosis 2.

What condition is associated with TSC2 p.Phe1806fs (c.5417_5418del)?

TSC2 p.Phe1806fs (c.5417_5418del) is associated with tuberous sclerosis 2 (ClinVar).

How common is TSC2 p.Phe1806fs (c.5417_5418del) in the general population?

TSC2 p.Phe1806fs (c.5417_5418del) 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.

TSC2 p.Phe1806fs

c.5417_5418del · rs2544521795 · VCV2993538

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

tuberous sclerosis 2

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	escapes	premature termination codon in the last exon (42 of 42) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -1.9, 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: TSC2
Protein: p.Phe1806fs
Coding: c.5417_5418del
MANE Select: NM_000548
dbSNP: rs2544521795
Type: Deletion
Location: chr16:2088602 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB

Full TSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tuberous sclerosis 2 — 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

TSC2 p.Phe1806Cys Uncertain significance ★★ ⚠ same residue
TSC2 p.Phe1806Ile Uncertain significance ★ ⚠ same residue
TSC2 p.Phe1806Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC2 c.1945_1946+4del Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.2355+2_2355+5del Pathogenic ★★ same condition
TSC2 c.5252_5259+19del Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.5259+1del Pathogenic/Likely pathogenic ★★ same condition
TSC2 p.Ala1169fs 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/tsc2-p-phe1806fs (accessed [today's date]).

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