Is MECP2 p.Ser161Phe (c.482C>T) pathogenic?

MECP2 p.Ser161Phe (c.482C>T) is classified Uncertain significance in MECP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely pathogenic (0.736); Very rare (popmax 0.000223%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MECP2 p.Ser161Phe (c.482C>T)?

MECP2 p.Ser161Phe (c.482C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MECP2 p.Ser161Phe (c.482C>T) in the general population?

MECP2 p.Ser161Phe (c.482C>T) is very rare (popmax 0.000223%, nfe) (gnomAD).

What do computational predictors say about MECP2 p.Ser161Phe (c.482C>T)?

AlphaMissense predicts likely pathogenic (score 0.736) — an in-silico prediction, not a clinical call.

MECP2 p.Ser161Phe

c.482C>T · VCV3293939

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000223%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.736	likely pathogenic
REVEL	0.762	pathogenic-leaning
SaProt	LLR -13.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.1, phastCons 1
Regional constraint	o/e 1.55	unconstrained · MANE · 1,052 bp · p 2.6e-22 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S149F vs ClinVar S161F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000223% European (non-Finnish) · 2/895,192 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000273% 3/1,097,812 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0021%	47,641
European (non-Finnish)grpmax	0.000223%	447,596

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser161Phe
Coding: c.482C>T
MANE Select: NM_001110792
Type: single nucleotide variant
Location: chrX:154031382 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 149 UniProt numbering: the mbd domain; a β-strand; 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

Similar variants

MECP2 p.Ser161= Likely benign ★★ same residue
MECP2 p.Ser161Tyr Uncertain significance ★ ⚠ same residue
MECP2 p.Arg118Gln Pathogenic/Likely pathogenic ★★ same condition
MECP2 p.Arg145Ser Likely pathogenic ★★ same condition
MECP2 p.Gln140Pro Pathogenic/Likely pathogenic ★★ same condition
MECP2 p.Gln31Ter Pathogenic ★★ same condition
MECP2 p.Gly16= Pathogenic ★★ same condition
MECP2 p.Ala289Val Uncertain significance ★★ ⚠ 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-ser161phe (accessed [today's date]).

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