Is TSC2 p.Val391del (c.1172_1174del) pathogenic?

TSC2 p.Val391del (c.11721174del) is classified Uncertain significance in TSC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-06-21). Absent from gnomAD; Associated with tuberous sclerosis 2.

What condition is associated with TSC2 p.Val391del (c.1172_1174del)?

TSC2 p.Val391del (c.1172_1174del) is associated with tuberous sclerosis 2, lymphangioleiomyomatosis, isolated focal cortical dysplasia type II (ClinVar).

How common is TSC2 p.Val391del (c.1172_1174del) in the general population?

TSC2 p.Val391del (c.1172_1174del) 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.

TSC2 p.Val391del

c.1172_1174del · rs1567428371 · VCV626197

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1

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.Val391del
Coding: c.1172_1174del
MANE Select: NM_000548
dbSNP: rs1567428371
Type: Deletion
Location: chr16:2061921 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 391: an α-helix; the 'required for interaction with tsc1' region

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

Also linked: lymphangioleiomyomatosis isolated focal cortical dysplasia type II

For Tuberous sclerosis complex (Orphanet):

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

Similar variants

TSC2 p.Val391Leu Uncertain significance ★★ same residue
TSC2 p.Val391= Likely benign ★★ same residue
TSC2 p.Val391Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC2 p.Val391Met Uncertain significance ★ ⚠ 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

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-val391del (accessed [today's date]).

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