Is MTOR p.Glu2015Asp (c.6045G>T) pathogenic?

MTOR p.Glu2015Asp (c.6045G>T) is classified Uncertain significance in MTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). AlphaMissense: likely pathogenic (0.9886); Very rare (popmax 8.48e-05%, nfe); Associated with MTOR-related disorder.

What condition is associated with MTOR p.Glu2015Asp (c.6045G>T)?

MTOR p.Glu2015Asp (c.6045G>T) is associated with MTOR-related disorder (ClinVar).

How common is MTOR p.Glu2015Asp (c.6045G>T) in the general population?

MTOR p.Glu2015Asp (c.6045G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MTOR p.Glu2015Asp (c.6045G>T)?

AlphaMissense predicts likely pathogenic (score 0.9886) — an in-silico prediction, not a clinical call.

MTOR p.Glu2015Asp

c.6045G>T · rs1642915683 · VCV2635154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

MTOR-related disorder

Computational evidence

Protein change
AlphaMissense	0.9886	likely pathogenic
REVEL	0.353	indeterminate
SaProt	LLR -13.12	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -0.59, phastCons 0.99
Regional constraint	o/e 0.42	unconstrained · MANE · 14 kb · p 6.9e-46 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,274 alleles

Overall 6.2e-05% 1/1,612,414 alleles · very rare exomes 1/1,460,088 · genomes 0/152,326 · 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: MTOR
Protein: p.Glu2015Asp
Coding: c.6045G>T
MANE Select: NM_004958
dbSNP: rs1642915683
Type: single nucleotide variant
Location: chr1:11127795 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 2015: an α-helix; the 'sufficient for interaction with the fkbp1a/rapamycin complex' region

Full MTOR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MTOR-related disorder

Similar variants

MTOR p.Glu2015Gln Uncertain significance ★ ⚠ same residue
MTOR p.Glu1799Lys Pathogenic ★★ ⚠ same condition
MTOR p.Asp1140Asn Uncertain significance ★★ ⚠ same condition
MTOR p.His236Arg Uncertain significance ★★ ⚠ same condition
MTOR p.Tyr929Cys Uncertain significance ★★ ⚠ same condition
MTOR p.Asp2102Glu Likely pathogenic ★ ⚠ same condition
MTOR p.Val2006Leu Likely pathogenic ★ ⚠ same condition
MTOR p.Ala492Ser 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-glu2015asp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown