Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 83.1%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax 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 -9.3 | GERP -3.1 |
| Overall | ||
| CADD | 1.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
83.1%
East Asian · 37,306/44,870 alleles
Filtering AF
82.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 82.1%
Overall
70.4%
1,135,304/1,613,390 alleles · common
exomes 1,049,597/1,461,392 · genomes 85,707/151,998 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 83.1% | 1 |
| Amishnot grpmax-eligible | 78.3% | 1 |
| European (non-Finnish) | 74.1% | 1 |
| Finnishnot grpmax-eligible | 72% | 1 |
| Admixed American | 70.2% | 1 |
| Middle Eastern | 68.4% | 1 |
| Remaining individualsnot grpmax-eligible | 68% | 1 |
| South Asian | 65.4% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 58.3% | 2 |
| African / African-American | 14.8% | 7 |
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.Ala1577=
- Coding
- c.4731G>A
- MANE Select
- NM_004958
- dbSNP
- rs1057079
- Type
- single nucleotide variant
- Location
- chr1:11145001 (GRCh38)
- Gene constraint
- LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.57 · 73 PDB
- Residue 1577
- an α-helix; the fat domain
Similar variants
- MTOR p.Ala1577Gly Uncertain significance ★ ⚠ same residue
- MTOR p.Cys1483Tyr Pathogenic ★★★ same condition
- MTOR p.Thr1977Lys Pathogenic ★★★ same condition
- MTOR p.Trp1490Arg Likely pathogenic ★★★ same condition
- MTOR p.Glu1799Lys Pathogenic ★★ ⚠ same condition
- MTOR p.Glu2419Lys Pathogenic ★★ same condition
- MTOR p.Met2327Ile Pathogenic ★★ same condition
- MTOR p.Phe1888Cys 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/mtor-p-ala1577 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown