Is MTOR p.Val2389Phe (c.7165G>T) pathogenic?

MTOR p.Val2389Phe (c.7165G>T) is classified Uncertain significance in MTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-26). AlphaMissense: likely pathogenic (0.9568); Absent from gnomAD v4.1; Associated with isolated focal cortical dysplasia type II.

What condition is associated with MTOR p.Val2389Phe (c.7165G>T)?

MTOR p.Val2389Phe (c.7165G>T) is associated with isolated focal cortical dysplasia type II (ClinVar).

How common is MTOR p.Val2389Phe (c.7165G>T) in the general population?

MTOR p.Val2389Phe (c.7165G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTOR p.Val2389Phe (c.7165G>T)?

AlphaMissense predicts likely pathogenic (score 0.9568) — an in-silico prediction, not a clinical call.

MTOR p.Val2389Phe

c.7165G>T · rs2100317284 · VCV3065102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9568 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

isolated focal cortical dysplasia type II

Computational evidence

Protein change
AlphaMissense	0.9568	likely pathogenic
REVEL	0.838	moderately pathogenic-leaning
SaProt	LLR -10.97	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Pangolin	Δ0.22	gain · loss 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 556 bp · p 8.3e-11 · regional, not allelic
Overall
CADD	34.0	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

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.Val2389Phe
Coding: c.7165G>T
MANE Select: NM_004958
dbSNP: rs2100317284
Type: single nucleotide variant
Location: chr1:11114453 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 2389: a turn; the pi3k/pi4k catalytic domain

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

Disease context

isolated focal cortical dysplasia type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Isolated focal cortical dysplasia (Orphanet):

Onset: All ages

Similar variants

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MTOR p.Ser2215Phe Pathogenic ★★★ same condition
MTOR p.Ser2215Tyr Pathogenic ★★★ same condition
MTOR p.Thr1977Lys Pathogenic ★★★ same condition
MTOR p.Ala1459Ser Uncertain significance ★★★ ⚠ same condition
MTOR p.Ala1459Asp Pathogenic ★★ same condition
MTOR p.Glu1799Lys 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-val2389phe (accessed [today's date]).

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