Is MTOR p.Ala204Pro (c.610G>C) pathogenic?

MTOR p.Ala204Pro (c.610G>C) is classified Uncertain significance in MTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-14). AlphaMissense: ambiguous (0.3956); Very rare (popmax 0.00167%, amr).

How common is MTOR p.Ala204Pro (c.610G>C) in the general population?

MTOR p.Ala204Pro (c.610G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MTOR p.Ala204Pro (c.610G>C)?

AlphaMissense predicts ambiguous (score 0.3956) — an in-silico prediction, not a clinical call.

MTOR p.Ala204Pro

c.610G>C · rs1253412423 · VCV1407806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3956 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.3956	ambiguous
REVEL	0.509	indeterminate
SaProt	LLR -7.22	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 2,506 bp · p 8.4e-18 · regional, not allelic
Overall
CADD	26.0	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 0.00167% Admixed American · 1/60,012 alleles

Overall 6.84e-05% 1/1,461,870 alleles · very rare

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.Ala204Pro
Coding: c.610G>C
MANE Select: NM_004958
dbSNP: rs1253412423
Type: single nucleotide variant
Location: chr1:11256087 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 204: an α-helix; the 'interaction with nbn' region

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

Similar variants

MTOR p.Ala204= Uncertain significance ★ same residue
MTOR p.Ala204Thr Uncertain significance ★ ⚠ 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-ala204pro (accessed [today's date]).

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