Is TSC2 p.Ser1799= (c.5397G>T) pathogenic?

TSC2 p.Ser1799= (c.5397G>T) is classified Benign/Likely benign in TSC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-09). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with TSC2 p.Ser1799= (c.5397G>T)?

TSC2 p.Ser1799= (c.5397G>T) is associated with hereditary neoplastic syndrome, tuberous sclerosis 2 (ClinVar).

How common is TSC2 p.Ser1799= (c.5397G>T) in the general population?

TSC2 p.Ser1799= (c.5397G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

TSC2 p.Ser1799=

c.5397G>T · rs1051771 · VCV1118494

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.3
Overall
CADD	0.002	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,066 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000311% 5/1,607,358 alleles · very rare exomes 4/1,455,180 · genomes 1/152,178 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,066
European (non-Finnish)	0.000339%	294,964

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.Ser1799=
Coding: c.5397G>T
MANE Select: NM_000548
dbSNP: rs1051771
Type: single nucleotide variant
Location: chr16:2088583 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 1799: a modified residue (phosphoserine)

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 2

Similar variants

TSC2 p.Ser1799Ala Uncertain significance ★★ ⚠ same residue
TSC2 p.Ser1799Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC2 p.Ser1799Trp Uncertain significance ★ ⚠ same residue
TSC2 p.Ser1799Pro Benign ★ ⚠ same residue
TSC2 p.Ser1799_Val1800insSer Uncertain significance ★★ same residue
TSC2 p.Ser1799del Conflicting classifications of pathogenicity ★ same residue
TSC2 c.1257+1G>A Pathogenic ★★ same condition
TSC2 c.1258-2A>G 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-ser1799 (accessed [today's date]).

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