TSC1 p.Ser334=
c.1002G>C · rs200820603 · VCV1118409
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
Conditions
2
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 -8.1 | GERP -3.9 |
| Overall | ||
| CADD | 1.006 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,179,732 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,613,558 alleles · very rare
exomes 2/1,461,610 · genomes 0/151,948 · joint denominator
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.Ser334=
- Coding
- c.1002G>C
- MANE Select
- NM_000368
- dbSNP
- rs200820603
- Type
- single nucleotide variant
- Location
- chr9:132911480 (GRCh38)
- Gene constraint
- LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.55 · 5 PDB
- Residue 334
- a UniProt-annotated variant site (in tsc1)
Similar variants
- TSC1 p.Ser334Trp Uncertain significance ★★ ⚠ same residue
- TSC1 p.Ser334Leu Benign/Likely benign ★★ same residue
- TSC1 p.Ser334Ter Pathogenic ★ same residue
- TSC1 p.Ser334Thr 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-ser334 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown