Is MTOR p.Asp302Val (c.905A>T) pathogenic?

MTOR p.Asp302Val (c.905A>T) is classified Likely benign in MTOR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). AlphaMissense: ambiguous (0.4618); Ultra-rare (popmax 0.0217%, amr); Associated with Inborn genetic diseases.

What condition is associated with MTOR p.Asp302Val (c.905A>T)?

MTOR p.Asp302Val (c.905A>T) is associated with Inborn genetic diseases (ClinVar).

How common is MTOR p.Asp302Val (c.905A>T) in the general population?

MTOR p.Asp302Val (c.905A>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about MTOR p.Asp302Val (c.905A>T)?

AlphaMissense predicts ambiguous (score 0.4618) — an in-silico prediction, not a clinical call.

MTOR p.Asp302Val

c.905A>T · rs761323069 · VCV663168

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4618 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4618	ambiguous
REVEL	0.182	moderately benign-leaning
SaProt	LLR -7.79	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 18 kb · p 7.9e-08 · regional, not allelic
Overall
CADD	25.2	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

Grpmax group 0.0217% Admixed American · 13/59,998 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00223% 36/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,615
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00178%	56,191

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.Asp302Val
Coding: c.905A>T
MANE Select: NM_004958
dbSNP: rs761323069
Type: single nucleotide variant
Location: chr1:11248030 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 302: 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 p.Asp302Asn Benign ★ 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-asp302val (accessed [today's date]).

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