Is TSC2 p.Asp817= (c.2451C>T) pathogenic?

TSC2 p.Asp817= (c.2451C>T) is classified Benign/Likely benign in TSC2 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-03). Rare (popmax 0.565%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with TSC2 p.Asp817= (c.2451C>T)?

TSC2 p.Asp817= (c.2451C>T) is associated with hereditary neoplastic syndrome, tuberous sclerosis, tuberous sclerosis 2 (ClinVar).

How common is TSC2 p.Asp817= (c.2451C>T) in the general population?

TSC2 p.Asp817= (c.2451C>T) is rare (popmax 0.565%, sas) (gnomAD).

TSC2 p.Asp817=

c.2451C>T · rs201442542 · VCV64991

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

rare (popmax 0.565%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.55	GERP -4.2, phastCons 0.002
Overall
CADD	7.208	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.565% South Asian · 515/91,078 alleles

Filtering AF 0.525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.509%

Overall 0.0508% 819/1,613,236 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.565%	177
Remaining individualsnot grpmax-eligible	0.0544%	1,838
Middle Eastern	0.0499%	2,004
European (non-Finnish)	0.0221%	4,521
African / African-American	0.004%	25,023
Admixed American	0.00333%	30,011
East Asian	0.00223%	44,890

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TSC2
Protein: p.Asp817=
Coding: c.2451C>T
MANE Select: NM_000548
dbSNP: rs201442542
Type: single nucleotide variant
Location: chr16:2074295 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 817: 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

Also linked: tuberous sclerosis tuberous sclerosis 2

Similar variants

TSC2 p.Asp817Asn Uncertain significance ★★ ⚠ same residue
TSC2 p.Asp817Ala Uncertain significance ★ ⚠ same residue
TSC2 p.Asp817Val Uncertain significance ★ ⚠ same residue
TSC2 c.1257+1G>A Pathogenic ★★ same condition
TSC2 c.1258-2A>G Pathogenic ★★ same condition
TSC2 c.1361+1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.1361+1G>T Pathogenic/Likely pathogenic ★★ same condition
TSC2 c.1362-1G>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-asp817 (accessed [today's date]).

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