MTOR p.Pro2273=
c.6819G>A · rs138151561 · VCV696427
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0961%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.40 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.5 |
| Overall | ||
| CADD | 0.153 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0961%
African / African-American · 72/74,910 alleles
Filtering AF
0.0783%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0717%
Overall
0.00719%
116/1,613,920 alleles · ultra-rare
exomes 70/1,461,744 · genomes 46/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0961% | 1,040 |
| Admixed American | 0.0117% | 8,571 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,620 |
| European (non-Finnish) | 0.00263% | 38,065 |
| South Asian | 0.0022% | 45,542 |
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.Pro2273=
- Coding
- c.6819G>A
- MANE Select
- NM_004958
- dbSNP
- rs138151561
- Type
- single nucleotide variant
- Location
- chr1:11121360 (GRCh38)
- Gene constraint
- LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.57 · 73 PDB
- Residue 2273
- a turn; the pi3k/pi4k catalytic domain; the 'interaction with mlst8' region
Similar variants
- MTOR p.Pro2273Leu Benign ★ same residue
- MTOR p.Ala1669Ser Likely pathogenic ★★★ ⚠ same type
- MTOR p.Cys1483Arg Pathogenic ★★★ same type
- MTOR p.Cys1483Tyr Pathogenic ★★★ same type
- MTOR p.Leu1460Pro Pathogenic ★★★ same type
- MTOR p.Leu2427Pro Pathogenic ★★★ same type
- MTOR p.Ser2215Phe Pathogenic ★★★ same type
- MTOR p.Ser2215Tyr Pathogenic ★★★ same type
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-pro2273 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown