Is MECP2 p.Ser362= (c.1086C>T) pathogenic?

MECP2 p.Ser362= (c.1086C>T) is classified Conflicting classifications of pathogenicity in MECP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-09-12). Ultra-rare (popmax 0.0689%, mid); Associated with Inborn genetic diseases.

What condition is associated with MECP2 p.Ser362= (c.1086C>T)?

MECP2 p.Ser362= (c.1086C>T) is associated with Inborn genetic diseases, severe neonatal-onset encephalopathy with microcephaly (ClinVar).

How common is MECP2 p.Ser362= (c.1086C>T) in the general population?

MECP2 p.Ser362= (c.1086C>T) is ultra-rare (popmax 0.0689%, mid) (gnomAD).

MECP2 p.Ser362=

c.1086C>T · rs1557136001 · VCV1152555

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0689%, mid)

Conditions

Inborn genetic diseases

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 4.1	GERP 0.46, phastCons 1
Overall
CADD	7.602	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0689% Middle Eastern · 3/4,354 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00996%

Overall 0.000827% 10/1,209,884 alleles · ultra-rare exomes 8/1,098,179 · genomes 2/111,705 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0689%	1,451
European (non-Finnish)	0.000782%	127,866

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: MECP2
Protein: p.Ser362=
Coding: c.1086C>T
MANE Select: NM_001110792
dbSNP: rs1557136001
Type: single nucleotide variant
Location: chrX:154030778 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 362: a UniProt-annotated variant site (in rtt); the 'disordered' region

Full MECP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe neonatal-onset encephalopathy with microcephaly

Similar variants

MECP2 p.Ser362Asn Uncertain significance ★ ⚠ same residue
MECP2 c.414-3C>G Pathogenic ★★★ same condition
MECP2 c.62+1G>A Pathogenic ★★★ same condition
MECP2 p.Ala291Val Likely pathogenic ★★★ ⚠ same condition
MECP2 p.Arg127His Pathogenic ★★★ same condition
MECP2 p.Arg145Cys Pathogenic ★★★ same condition
MECP2 p.Arg145His Pathogenic ★★★ same condition
MECP2 p.Arg179Trp 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/mecp2-p-ser362 (accessed [today's date]).

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