Is MTOR p.Ala352Ser (c.1054G>T) pathogenic?

MTOR p.Ala352Ser (c.1054G>T) is classified Uncertain significance in MTOR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-25). AlphaMissense: likely benign (0.0676); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MTOR p.Ala352Ser (c.1054G>T)?

MTOR p.Ala352Ser (c.1054G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MTOR p.Ala352Ser (c.1054G>T) in the general population?

MTOR p.Ala352Ser (c.1054G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTOR p.Ala352Ser (c.1054G>T)?

AlphaMissense predicts likely benign (score 0.0676) — an in-silico prediction, not a clinical call.

MTOR p.Ala352Ser

c.1054G>T · rs2100939918 · VCV2486985

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0676 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0676	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.6, phastCons 0.52
Regional constraint	o/e 0.77	unconstrained · MANE · 18 kb · p 7.9e-08 · regional, not allelic
Overall
CADD	16.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Ala352Ser
Coding: c.1054G>T
MANE Select: NM_004958
dbSNP: rs2100939918
Type: single nucleotide variant
Location: chr1:11247881 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 352: the 'interaction with nbn' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTOR c.5365-5A>G Uncertain significance ★★ same condition
MTOR p.Arg1818Cys Uncertain significance ★★ ⚠ same condition
MTOR p.Arg2060Gln Uncertain significance ★★ ⚠ same condition
MTOR p.Arg2110Gln Uncertain significance ★★ ⚠ same condition
MTOR p.Arg2217Gln Uncertain significance ★★ ⚠ same condition
MTOR p.Arg2445Gly Uncertain significance ★★ same condition
MTOR p.Arg2503Ser Uncertain significance ★★ ⚠ same condition
MTOR p.Arg814Lys Uncertain significance ★★ ⚠ 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-ala352ser (accessed [today's date]).

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