Is TSC1 p.Ser598= (c.1794C>T) pathogenic?

TSC1 p.Ser598= (c.1794C>T) is classified Conflicting classifications of pathogenicity in TSC1 (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2025-11-25). Very rare (popmax 0.00267%, afr); Associated with tuberous sclerosis 1.

What condition is associated with TSC1 p.Ser598= (c.1794C>T)?

TSC1 p.Ser598= (c.1794C>T) is associated with tuberous sclerosis 1, tuberous sclerosis, lymphangioleiomyomatosis (ClinVar).

How common is TSC1 p.Ser598= (c.1794C>T) in the general population?

TSC1 p.Ser598= (c.1794C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Tuberous sclerosis complex inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TSC1 p.Ser598=

c.1794C>T · rs766438395 · VCV220765

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

tuberous sclerosis 1

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 -0.096	GERP -4.2, phastCons 0.006
Overall
CADD	5.108	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,912 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,614,066 alleles · very rare exomes 6/1,461,886 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,456
East Asian	0.00223%	44,902
South Asian	0.0011%	91,090
European (non-Finnish)	0.000339%	295,011

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: TSC1
Protein: p.Ser598=
Coding: c.1794C>T
MANE Select: NM_000368
dbSNP: rs766438395
Type: single nucleotide variant
Location: chr9:132905784 (GRCh38)
Gene constraint: LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.55 · 5 PDB
Residue 598: the 'mediates interaction with wdr45b' region; a modified residue (phosphoserine); a UniProt-annotated variant site (in tsc1)

Full TSC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tuberous sclerosis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tuberous sclerosis lymphangioleiomyomatosis isolated focal cortical dysplasia type II hereditary neoplastic syndrome

For Tuberous sclerosis complex (Orphanet):

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

Similar variants

TSC1 p.Ser598Arg Uncertain significance ★★ ⚠ same residue
TSC1 p.Ser598Asn Uncertain significance ★★ ⚠ same residue
TSC1 p.Ser598Gly Uncertain significance ★ ⚠ same residue
TSC1 p.Ser598Ile Uncertain significance ★ ⚠ same residue
TSC1 c.1029+1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.1029+1G>C Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.107-1G>A Pathogenic/Likely pathogenic ★★ same condition
TSC1 c.1141+1G>A 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/tsc1-p-ser598 (accessed [today's date]).

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