Is TSC2 p.Arg413= (c.1239A>G) pathogenic?

TSC2 p.Arg413= (c.1239A>G) is classified Uncertain significance in TSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-26). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TSC2 p.Arg413= (c.1239A>G)?

TSC2 p.Arg413= (c.1239A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is TSC2 p.Arg413= (c.1239A>G) in the general population?

TSC2 p.Arg413= (c.1239A>G) is absent from gnomAD v4.1 (gnomAD).

TSC2 p.Arg413=

c.1239A>G · VCV4866117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.98	donor gain · deltas
Pangolin	Δ0.79	gain · loss 0.39 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.077	GERP -3.7, phastCons 0.06
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TSC2
Protein: p.Arg413=
Coding: c.1239A>G
MANE Select: NM_000548
Type: single nucleotide variant
Location: chr16:2061990 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 413: an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TSC2 p.Arg413Gly Uncertain significance ★★ ⚠ same residue
TSC2 p.Arg413Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC2 c.1443+2T>C Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.1443+5G>C Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.1599+1G>A Pathogenic ★★ same condition
TSC2 c.1716+1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.1947-2A>C Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.2098-1G>A 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-arg413 (accessed [today's date]).

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