Is MTOR p.Pro765= (c.2295C>A) pathogenic?

MTOR p.Pro765= (c.2295C>A) is classified Uncertain significance in MTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-28). Absent from gnomAD v4.1; Associated with macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome.

How common is MTOR p.Pro765= (c.2295C>A) in the general population?

MTOR p.Pro765= (c.2295C>A) is absent from gnomAD v4.1 (gnomAD).

MTOR p.Pro765=

Q: What condition is associated with MTOR p.Pro765= (c.2295C>A)?

MTOR p.Pro765= (c.2295C>A) is associated with macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (ClinVar).

c.2295C>A · rs2523286401 · VCV2433825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -0.52, phastCons 0.87
Overall
CADD	4.428	PHRED · no single calibrated threshold — expert panels disagree

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.Pro765=
Coding: c.2295C>A
MANE Select: NM_004958
dbSNP: rs2523286401
Type: single nucleotide variant
Location: chr1:11234179 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 765: an α-helix

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

Disease context

macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTOR p.Cys1483Tyr Pathogenic ★★★ same condition
MTOR p.Thr1977Lys Pathogenic ★★★ same condition
MTOR p.Trp1490Arg Likely pathogenic ★★★ same condition
MTOR p.Glu1799Lys Pathogenic ★★ ⚠ same condition
MTOR p.Glu2419Lys Pathogenic ★★ same condition
MTOR p.Met2327Ile Pathogenic ★★ same condition
MTOR p.Phe1888Cys Pathogenic/Likely pathogenic ★★ same condition
MTOR p.Ser2413Ile 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-pro765 (accessed [today's date]).

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