Is MTOR p.Met970Val (c.2908A>G) pathogenic?

MTOR p.Met970Val (c.2908A>G) is classified Uncertain significance in MTOR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-18). AlphaMissense: likely benign (0.2769); Very rare (popmax 0.00401%, afr); Associated with Inborn genetic diseases.

What condition is associated with MTOR p.Met970Val (c.2908A>G)?

MTOR p.Met970Val (c.2908A>G) is associated with Inborn genetic diseases (ClinVar).

How common is MTOR p.Met970Val (c.2908A>G) in the general population?

MTOR p.Met970Val (c.2908A>G) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about MTOR p.Met970Val (c.2908A>G)?

AlphaMissense predicts likely benign (score 0.2769) — an in-silico prediction, not a clinical call.

MTOR p.Met970Val

c.2908A>G · rs1349280110 · VCV945748

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2769 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2769	likely benign
REVEL	0.336	indeterminate
SaProt	LLR -5.20	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 26 kb · p 2.5e-27 · regional, not allelic
Overall
CADD	24.1	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

Grpmax group 0.00401% African / African-American · 3/74,864 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000496% 8/1,613,950 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,955
Admixed American	0.00167%	59,996
European (non-Finnish)	0.000339%	294,999

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.Met970Val
Coding: c.2908A>G
MANE Select: NM_004958
dbSNP: rs1349280110
Type: single nucleotide variant
Location: chr1:11228790 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 970: an α-helix

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 p.Met970Thr Uncertain significance ★ same residue
MTOR c.5365-5A>G Uncertain significance ★★ same condition
MTOR p.Ala352Ser 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

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-met970val (accessed [today's date]).

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