Is MTOR p.Ala711Pro (c.2131G>C) pathogenic?

MTOR p.Ala711Pro (c.2131G>C) is classified Uncertain significance in MTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-31). AlphaMissense: likely pathogenic (0.9987); Very rare (popmax 8.47e-05%, nfe).

How common is MTOR p.Ala711Pro (c.2131G>C) in the general population?

MTOR p.Ala711Pro (c.2131G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about MTOR p.Ala711Pro (c.2131G>C)?

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

MTOR p.Ala711Pro

c.2131G>C · rs2100898443 · VCV2748602

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic · top 5% in MTOR
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -15.44	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 26 kb · p 2.5e-27 · regional, not allelic
Overall
CADD	27.6	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 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 0.000124% 2/1,614,146 alleles · very rare exomes 2/1,461,852 · genomes 0/152,294 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)grpmax	8.47e-05%	1,180,030

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala711Pro
Coding: c.2131G>C
MANE Select: NM_004958
dbSNP: rs2100898443
Type: single nucleotide variant
Location: chr1:11237920 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 711: an α-helix

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

Similar variants

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
MTOR p.Ser2215Tyr Pathogenic ★★★ same type
MTOR p.Thr1977Arg 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-ala711pro (accessed [today's date]).

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