Is MBD4 p.Ser413fs (c.1237dup) pathogenic?

MBD4 p.Ser413fs (c.1237dup) is classified Pathogenic in MBD4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-09). Associated with tumor predisposition syndrome 2.

What condition is associated with MBD4 p.Ser413fs (c.1237dup)?

MBD4 p.Ser413fs (c.1237dup) is associated with tumor predisposition syndrome 2 (ClinVar).

How is MBD4-related tumor predisposition syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MBD4 p.Ser413fs

c.1237dup · VCV4052217

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

tumor predisposition syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1

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

Variant & gene context

Gene: MBD4
Protein: p.Ser413fs
Coding: c.1237dup
MANE Select: NM_001276270
Type: Duplication
Location: chr3:129434082 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.67 · 19 PDB
Residue 413: a UniProt-annotated variant site (in tpds2; no mbd4 protein detected by immunohistochemical analysis in patient tumor tissue); a UniProt-annotated variant site (in uvm1); a UniProt-annotated variant site (in tpds2)

Full MBD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tumor predisposition syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MBD4-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult

Similar variants

MBD4 p.Asn206Ter Pathogenic ★★ same condition
MBD4 p.Glu314fs Pathogenic/Likely pathogenic ★★ same condition
MBD4 p.Thr77fs Pathogenic ★★ same condition
MBD4 p.Ser413= Uncertain significance ★★ same residue
MBD4 p.Ser413Cys Uncertain significance ★★ ⚠ same residue
MBD4 p.Ile237fs Pathogenic ★ same condition
MBD4 p.Ser282fs Pathogenic ★ same condition
MBD4 c.335+9dup Likely benign ★ 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/mbd4-p-ser413fs (accessed [today's date]).

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