TSC1 p.Phe199=
c.597C>T · rs202242304 · VCV416683
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
Conditions
5
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.37 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -2.5 | GERP -4.2 |
| Overall | ||
| CADD | 12.22 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,884 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000805%
13/1,614,152 alleles · very rare
exomes 10/1,461,874 · genomes 3/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,961 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,253 |
| African / African-American | 0.00267% | 37,517 |
| South Asian | 0.0022% | 45,540 |
| Admixed American | 0.00167% | 60,026 |
| European (non-Finnish) | 0.000254% | 393,338 |
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.Phe199=
- Coding
- c.597C>T
- MANE Select
- NM_000368
- dbSNP
- rs202242304
- Type
- single nucleotide variant
- Location
- chr9:132921885 (GRCh38)
- Gene constraint
- LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.55 · 5 PDB
- Residue 199
- a UniProt-annotated variant site (in tsc1); a UniProt-annotated variant site (in tsc1; reduced expression; altered subcellular localization; reduced interaction with tsc2; reduced inhibition of torc1 signaling); an α-helix
Similar variants
- TSC1 p.Phe199Leu 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
- TSC1 c.1264-1G>A Pathogenic/Likely pathogenic ★★ same condition
- TSC1 c.1439-1G>A Pathogenic/Likely pathogenic ★★ same condition
- TSC1 c.1997+1G>A Pathogenic/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-phe199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown