Is MTOR p.Arg910Trp (c.2728C>T) pathogenic?

MTOR p.Arg910Trp (c.2728C>T) is classified Benign in MTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-15). AlphaMissense: ambiguous (0.3752); Very rare (popmax 0.00439%, sas).

How common is MTOR p.Arg910Trp (c.2728C>T) in the general population?

MTOR p.Arg910Trp (c.2728C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about MTOR p.Arg910Trp (c.2728C>T)?

AlphaMissense predicts ambiguous (score 0.3752) — an in-silico prediction, not a clinical call.

MTOR p.Arg910Trp

c.2728C>T · rs200143518 · VCV950835

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3752 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3752	ambiguous
REVEL	0.263	benign-leaning
SaProt	LLR -9.24	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 26 kb · p 2.5e-27 · regional, not allelic
Overall
CADD	29.3	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 0.00439% South Asian · 4/91,076 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.0013% 21/1,613,976 alleles · very rare exomes 18/1,461,832 · genomes 3/152,144 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,769
African / African-American	0.004%	24,970
East Asian	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.00102%	98,334

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.Arg910Trp
Coding: c.2728C>T
MANE Select: NM_004958
dbSNP: rs200143518
Type: single nucleotide variant
Location: chr1:11230976 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB

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

Similar variants

MTOR p.Arg910Gln Uncertain significance ★★ ⚠ same residue
MTOR p.Arg910= 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

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-arg910trp (accessed [today's date]).

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