TSC2 p.Phe690=
c.2070C>T · rs558292668 · VCV1785391
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00228%, eas)
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 -0.38 | GERP -1.3, phastCons 0.001 |
| Overall | ||
| CADD | 4.511 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00228%
East Asian · 1/43,932 alleles
Overall
6.27e-05%
1/1,593,922 alleles · very rare
exomes 0/1,441,534 · genomes 1/152,388 · 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
- TSC2
- Protein
- p.Phe690=
- Coding
- c.2070C>T
- MANE Select
- NM_000548
- dbSNP
- rs558292668
- Type
- single nucleotide variant
- Location
- chr16:2071907 (GRCh38)
- Gene constraint
- LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.81 · 2 PDB
- Residue 690
- an α-helix
Similar variants
- TSC2 p.Phe690Leu Uncertain significance ★★ ⚠ same residue
- TSC2 p.Phe690Val 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
- TSC2 c.138+2T>C 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-phe690 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown