Is MTOR p.Arg1002Ter (c.3004C>T) pathogenic?

MTOR p.Arg1002Ter (c.3004C>T) is classified Uncertain significance in MTOR (ClinVar, Expert panel, 1 submitter; last evaluated 2025-06-06). Very rare (popmax 0.00133%, afr); Associated with overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes.

How common is MTOR p.Arg1002Ter (c.3004C>T) in the general population?

MTOR p.Arg1002Ter (c.3004C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

MTOR p.Arg1002Ter

Q: What condition is associated with MTOR p.Arg1002Ter (c.3004C>T)?

MTOR p.Arg1002Ter (c.3004C>T) is associated with overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (ClinVar).

c.3004C>T · rs770601118 · VCV1296995

Uncertain significance Expert panel

Classification

Uncertain significance

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

ClinGen expert panel

Uncertain Significance — Brain Malformations VCEP (overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes).

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 19 of 58
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP -0.66, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,040 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000274% 4/1,461,812 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,040
South Asian	0.0011%	91,076
European (non-Finnish)	0.000169%	589,998

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.Arg1002Ter
Coding: c.3004C>T
MANE Select: NM_004958
dbSNP: rs770601118
Type: single nucleotide variant
Location: chr1:11228694 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 1002: an α-helix

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

Disease context

overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTOR p.Arg1002Gln Uncertain significance ★★ ⚠ same residue
MTOR p.Arg1002= Likely benign ★ same residue
MTOR p.Ala1669Ser Likely pathogenic ★★★ ⚠ same condition
MTOR p.Cys1483Arg Pathogenic ★★★ same condition
MTOR p.Cys1483Tyr Pathogenic ★★★ same condition
MTOR p.Leu1460Pro Pathogenic ★★★ same condition
MTOR p.Leu2427Pro Pathogenic ★★★ same condition
MTOR p.Ser2215Phe Pathogenic ★★★ 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-arg1002ter (accessed [today's date]).

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