Is MTOR p.Ala134Val (c.401C>T) pathogenic?

MTOR p.Ala134Val (c.401C>T) is classified Uncertain significance in MTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-17). AlphaMissense: likely pathogenic (0.6728); Absent from gnomAD v4.1.

How common is MTOR p.Ala134Val (c.401C>T) in the general population?

MTOR p.Ala134Val (c.401C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTOR p.Ala134Val (c.401C>T)?

AlphaMissense predicts likely pathogenic (score 0.6728) — an in-silico prediction, not a clinical call.

MTOR p.Ala134Val

c.401C>T · rs2100978459 · VCV1305751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6728 · 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	0.6728	likely pathogenic
REVEL	0.336	indeterminate
SaProt	LLR -6.91	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 2,506 bp · p 8.4e-18 · regional, not allelic
Overall
CADD	27.0	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.Ala134Val
Coding: c.401C>T
MANE Select: NM_004958
dbSNP: rs2100978459
Type: single nucleotide variant
Location: chr1:11257036 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 134: an α-helix; the 'interaction with nbn' region

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

Similar variants

MTOR p.Ala134= Likely benign ★ 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
MTOR p.Ser2215Tyr 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-ala134val (accessed [today's date]).

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