Is MECP2 p.Ser176= (c.528C>T) pathogenic?

MECP2 p.Ser176= (c.528C>T) is classified Likely benign in MECP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-28). Absent from gnomAD v4.1.

How common is MECP2 p.Ser176= (c.528C>T) in the general population?

MECP2 p.Ser176= (c.528C>T) is absent from gnomAD v4.1 (gnomAD).

MECP2 p.Ser176=

c.528C>T · rs1557136964 · VCV496281

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 5.5	GERP 0.24, phastCons 1
Overall
CADD	9.341	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: MECP2
Protein: p.Ser176=
Coding: c.528C>T
MANE Select: NM_001110792
dbSNP: rs1557136964
Type: single nucleotide variant
Location: chrX:154031336 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 176: the 'disordered' region

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

Similar variants

MECP2 p.Ser176Arg Uncertain significance ★ ⚠ same residue
MECP2 p.Ser176Gly Uncertain significance ★ ⚠ same residue
MECP2 c.414-3C>G Pathogenic ★★★ same type
MECP2 c.62+1G>A Pathogenic ★★★ same type
MECP2 c.62+2T>G Pathogenic ★★★ same type
MECP2 p.Ala143Asp Pathogenic ★★★ same type
MECP2 p.Ala291Val Likely pathogenic ★★★ ⚠ same type
MECP2 p.Arg127His 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/mecp2-p-ser176 (accessed [today's date]).

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