Is MTOR p.Arg1987Pro (c.5960G>C) pathogenic?

MTOR p.Arg1987Pro (c.5960G>C) is classified Uncertain significance in MTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-26). AlphaMissense: likely pathogenic (0.9987); Absent from gnomAD v4.1.

How common is MTOR p.Arg1987Pro (c.5960G>C) in the general population?

MTOR p.Arg1987Pro (c.5960G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTOR p.Arg1987Pro (c.5960G>C)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

MTOR p.Arg1987Pro

c.5960G>C · rs2100413784 · VCV2849805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic · top 5% in MTOR
REVEL	0.851	moderately pathogenic-leaning
SaProt	LLR -18.06	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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 0.42	unconstrained · MANE · 14 kb · p 6.9e-46 · regional, not allelic
Overall
CADD	26.5	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.Arg1987Pro
Coding: c.5960G>C
MANE Select: NM_004958
dbSNP: rs2100413784
Type: single nucleotide variant
Location: chr1:11128077 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 1987: an α-helix

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

Similar variants

MTOR p.Arg1987Gln Uncertain significance ★ ⚠ same residue
MTOR p.Arg1987Trp 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-arg1987pro (accessed [today's date]).

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