MTOR p.Ser2221=
c.6663C>T · rs765034247 · VCV972411
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00314%, nfe)
Conditions
1
Inborn genetic diseases
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 6.6 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 13.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00314%
European (non-Finnish) · 37/1,180,038 alleles
Filtering AF
0.00231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00202%
Overall
0.00229%
37/1,614,118 alleles · very rare
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
- MTOR
- Protein
- p.Ser2221=
- Coding
- c.6663C>T
- MANE Select
- NM_004958
- dbSNP
- rs765034247
- Type
- single nucleotide variant
- Location
- chr1:11122126 (GRCh38)
- Gene constraint
- LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.57 · 73 PDB
- Residue 2221
- the pi3k/pi4k catalytic domain
Similar variants
- MTOR c.5365-5A>G Uncertain significance ★★ same condition
- MTOR p.Ala352Ser Uncertain significance ★★ ⚠ same condition
- MTOR p.Arg1818Cys Uncertain significance ★★ ⚠ same condition
- MTOR p.Arg2060Gln Uncertain significance ★★ ⚠ same condition
- MTOR p.Arg2110Gln Uncertain significance ★★ ⚠ same condition
- MTOR p.Arg2217Gln Uncertain significance ★★ ⚠ same condition
- MTOR p.Arg2445Gly Uncertain significance ★★ same condition
- MTOR p.Arg2503Ser Uncertain significance ★★ ⚠ 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/mtor-p-ser2221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown