Is MECP2 p.Ser82= (c.246C>T) pathogenic?

MECP2 p.Ser82= (c.246C>T) is classified Benign/Likely benign in MECP2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-17). Rare (popmax 0.329%, afr); Associated with History of neurodevelopmental disorder.

How common is MECP2 p.Ser82= (c.246C>T) in the general population?

MECP2 p.Ser82= (c.246C>T) is rare (popmax 0.329%, afr) (gnomAD).

MECP2 p.Ser82=

Q: What condition is associated with MECP2 p.Ser82= (c.246C>T)?

MECP2 p.Ser82= (c.246C>T) is associated with History of neurodevelopmental disorder, X-linked intellectual disability-psychosis-macroorchidism syndrome, syndromic X-linked intellectual disability Lubs type (ClinVar).

c.246C>T · rs61754439 · VCV138186

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.329%, afr)

Conditions

History of neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.5	GERP -3.4
Overall
CADD	0.557	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.329% African / African-American · 190/57,742 alleles

Filtering AF 0.291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.276%

Overall 0.0331% 401/1,211,438 alleles · rare exomes 277/1,098,089 · genomes 124/113,349 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.329%	304
Middle Eastern	0.115%	868
Admixed American	0.109%	921
Remaining individualsnot grpmax-eligible	0.0441%	2,268
European (non-Finnish)	0.0145%	6,888
South Asian	0.00527%	18,983
East Asian	0.00296%	33,797
Finnishnot grpmax-eligible	0.00214%	46,765

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.Ser82=
Coding: c.246C>T
MANE Select: NM_001110792
dbSNP: rs61754439
Type: single nucleotide variant
Location: chrX:154032374 (GRCh38)
Structure: AlphaFold pLDDT 57.25 · 11 PDB
Residue 82: the 'disordered' region

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

Disease context

History of neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked intellectual disability-psychosis-macroorchidism syndrome syndromic X-linked intellectual disability Lubs type autism, susceptibility to, X-linked 3 severe neonatal-onset encephalopathy with microcephaly Rett syndrome

Similar variants

MECP2 p.Ser82Pro Uncertain significance ★★★ ⚠ same residue
MECP2 p.Ser82Cys Uncertain significance ★ ⚠ same residue
MECP2 c.414-3C>G Pathogenic ★★★ same condition
MECP2 c.62+1G>A Pathogenic ★★★ same condition
MECP2 c.62+2T>G Pathogenic ★★★ same condition
MECP2 p.Ala143Asp Pathogenic ★★★ same condition
MECP2 p.Ala291Val Likely pathogenic ★★★ ⚠ same condition
MECP2 p.Arg127His 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-ser82 (accessed [today's date]).

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