MTOR p.Ala40=
c.120C>T · rs375256941 · VCV1130406
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00935%, afr)
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 -3.7 | GERP -3.3 |
| Overall | ||
| CADD | 4.794 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00935%
African / African-American · 7/74,884 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0031%
Overall
0.0039%
63/1,613,838 alleles · very rare
exomes 55/1,461,644 · genomes 8/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00935% | 10,698 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,618 |
| European (non-Finnish) | 0.00441% | 22,691 |
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.Ala40=
- Coding
- c.120C>T
- MANE Select
- NM_004958
- dbSNP
- rs375256941
- Type
- single nucleotide variant
- Location
- chr1:11259290 (GRCh38)
- Gene constraint
- LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.57 · 73 PDB
- Residue 40
- an α-helix; the 'interaction with nbn' region
Similar variants
- MTOR p.Ala40Val Uncertain significance ★ ⚠ same residue
- MTOR p.Ala40Thr Likely 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
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-ala40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown