MTOR p.Ser1851=

Q: Is MTOR p.Ser1851= (c.5553C>T) pathogenic?

MTOR p.Ser1851= (c.5553C>T) is classified Benign in MTOR (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 45.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome.

Q: What condition is associated with MTOR p.Ser1851= (c.5553C>T)?

MTOR p.Ser1851= (c.5553C>T) is associated with macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (ClinVar).

Q: How common is MTOR p.Ser1851= (c.5553C>T) in the general population?

MTOR p.Ser1851= (c.5553C>T) is common (popmax 45.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5553C>T · rs2275527 · VCV380311

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 45.2%, afr) — too common for a highly-penetrant pathogenic allele

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 -3.9	GERP -3.1
Overall
CADD	0.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 45.2% African / African-American · 33,789/74,798 alleles

Filtering AF 44.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 44.6%

Overall 23.6% 381,240/1,613,296 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	45.2%	2
Ashkenazi Jewishnot grpmax-eligible	32.6%	3
Middle Eastern	24.9%	4
European (non-Finnish)	23.6%	4
Remaining individualsnot grpmax-eligible	23.6%	4
Finnishnot grpmax-eligible	22.5%	4
Amishnot grpmax-eligible	19.1%	5
South Asian	16.7%	6
Admixed American	14.2%	7
East Asian	9.57%	10

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.Ser1851=
Coding: c.5553C>T
MANE Select: NM_004958
dbSNP: rs2275527
Type: single nucleotide variant
Location: chr1:11130589 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 73 PDB
Residue 1851: the fat domain; the 'disordered' region

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.Ser1851Thr Uncertain significance ★ ⚠ same residue
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

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-ser1851 (accessed [today's date]).

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