Is MTOR p.Arg766Pro (c.2297G>C) pathogenic?

MTOR p.Arg766Pro (c.2297G>C) is classified Uncertain significance in MTOR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-21). AlphaMissense: likely pathogenic (0.9541); Absent from gnomAD v4.1.

How common is MTOR p.Arg766Pro (c.2297G>C) in the general population?

MTOR p.Arg766Pro (c.2297G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTOR p.Arg766Pro (c.2297G>C)?

AlphaMissense predicts likely pathogenic (score 0.9541) — an in-silico prediction, not a clinical call.

MTOR p.Arg766Pro

c.2297G>C · rs1647117277 · VCV2580750

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9541 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9541	likely pathogenic
REVEL	0.63	indeterminate
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 26 kb · p 2.5e-27 · regional, not allelic
Overall
CADD	26.0	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.Arg766Pro
Coding: c.2297G>C
MANE Select: NM_004958
dbSNP: rs1647117277
Type: single nucleotide variant
Location: chr1:11234177 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 766: an α-helix

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

Similar variants

MTOR p.Arg766Ter Uncertain significance ★ same residue
MTOR p.Arg766fs Uncertain significance ★ 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-arg766pro (accessed [today's date]).

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