Is MTOR p.Ile2153Val (c.6457A>G) pathogenic?

MTOR p.Ile2153Val (c.6457A>G) is classified Likely pathogenic in MTOR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-08). AlphaMissense: likely benign (0.3359); Absent from gnomAD v4.1; Associated with macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome.

How common is MTOR p.Ile2153Val (c.6457A>G) in the general population?

MTOR p.Ile2153Val (c.6457A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTOR p.Ile2153Val (c.6457A>G)?

AlphaMissense predicts likely benign (score 0.3359) — an in-silico prediction, not a clinical call.

MTOR p.Ile2153Val

Q: What condition is associated with MTOR p.Ile2153Val (c.6457A>G)?

MTOR p.Ile2153Val (c.6457A>G) is associated with macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (ClinVar).

c.6457A>G · rs2100396600 · VCV1339560

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3359 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

Computational evidence

Protein change
AlphaMissense	0.3359	likely benign ⚠ discordant with ClinVar
REVEL	0.735	pathogenic-leaning
SaProt	LLR -9.75	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 14 kb · p 6.9e-46 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MTOR
Protein: p.Ile2153Val
Coding: c.6457A>G
MANE Select: NM_004958
dbSNP: rs2100396600
Type: single nucleotide variant
Location: chr1:11126691 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 2153: a β-strand

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

Disease context

macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
MTOR p.Ser2413Ile 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-ile2153val (accessed [today's date]).

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