Is TSC2 p.Arg313fs (c.936_951del) pathogenic?

TSC2 p.Arg313fs (c.936951del) is classified Likely pathogenic in TSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-28). Associated with TSC2-related disorder.

What condition is associated with TSC2 p.Arg313fs (c.936_951del)?

TSC2 p.Arg313fs (c.936_951del) is associated with TSC2-related disorder (ClinVar).

TSC2 p.Arg313fs

c.936_951del · VCV4927427

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

TSC2-related disorder

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 10 of 42
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1

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

Variant & gene context

Gene: TSC2
Protein: p.Arg313fs
Coding: c.936_951del
MANE Select: NM_000548
Type: Deletion
Location: chr16:2058834 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 313: the 'required for interaction with tsc1' region

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

Disease context

TSC2-related disorder

Similar variants

TSC2 p.Gly1472fs Pathogenic ★★ same condition
TSC2 p.Met276fs Pathogenic ★★ same condition
TSC2 p.Ser428del Pathogenic/Likely pathogenic ★★ same condition
TSC2 p.Tyr1250fs Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.5161-36_5215del Likely pathogenic ★ same condition
TSC2 p.Ala1124fs Likely pathogenic ★ same condition
TSC2 p.Gln1392fs Pathogenic ★ same condition
TSC2 p.Ile1797fs 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-arg313fs (accessed [today's date]).

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