Is MBD5 p.Cys46= (c.138C>T) pathogenic?

MBD5 p.Cys46= (c.138C>T) is classified Uncertain significance in MBD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). Absent from gnomAD v4.1; Associated with intellectual disability, autosomal dominant 1.

What condition is associated with MBD5 p.Cys46= (c.138C>T)?

MBD5 p.Cys46= (c.138C>T) is associated with intellectual disability, autosomal dominant 1 (ClinVar).

How common is MBD5 p.Cys46= (c.138C>T) in the general population?

MBD5 p.Cys46= (c.138C>T) is absent from gnomAD v4.1 (gnomAD).

MBD5 p.Cys46=

c.138C>T · rs2469807780 · VCV2827419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual disability, autosomal dominant 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	acceptor gain · deltas
Pangolin	Δ0.26	loss · gain 0.22 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Overall
CADD	17.32	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: MBD5
Protein: p.Cys46=
Coding: c.138C>T
MANE Select: NM_001378120
dbSNP: rs2469807780
Type: single nucleotide variant
Location: chr2:148462606 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.20
Residue 46: the mbd domain

Full MBD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal dominant 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MBD5 p.Cys46Arg Uncertain significance ★ ⚠ same residue
MBD5 c.397+1G>A Pathogenic ★★ same condition
MBD5 c.397+2T>C Pathogenic ★★ same condition
MBD5 p.Arg1440Ter Pathogenic ★★ same condition
MBD5 p.Arg200Ter Pathogenic ★★ same condition
MBD5 p.Arg325Ter Pathogenic/Likely pathogenic ★★ same condition
MBD5 p.Cys60Ter Pathogenic ★★ same condition
MBD5 p.Gln587Ter 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/mbd5-p-cys46 (accessed [today's date]).

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