Is MBD5 p.Ser40fs (c.117dup) pathogenic?

MBD5 p.Ser40fs (c.117dup) is classified Pathogenic in MBD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). Associated with intellectual disability, autosomal dominant 1.

What condition is associated with MBD5 p.Ser40fs (c.117dup)?

MBD5 p.Ser40fs (c.117dup) is associated with intellectual disability, autosomal dominant 1 (ClinVar).

MBD5 p.Ser40fs

c.117dup · VCV4715740

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual disability, autosomal dominant 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 0.97, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: MBD5
Protein: p.Ser40fs
Coding: c.117dup
MANE Select: NM_001378120
Type: Duplication
Location: chr2:148462582 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.20
Residue 40: 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.Lys1719fs Uncertain significance ★★ same condition
MBD5 p.Ala1244fs Pathogenic ★ same condition
MBD5 p.Arg200fs Pathogenic ★ same condition
MBD5 p.Arg501fs Pathogenic ★ same condition
MBD5 p.Cys60fs Pathogenic ★ same condition
MBD5 p.Cys66fs Pathogenic ★ same condition
MBD5 p.Glu65fs Pathogenic ★ same condition
MBD5 p.Ile107fs Likely 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-ser40fs (accessed [today's date]).

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