Is MBD4 p.Ser112= (c.336C>T) pathogenic?

MBD4 p.Ser112= (c.336C>T) is classified Conflicting classifications of pathogenicity in MBD4 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-06-08). Rare (popmax 0.132%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MBD4 p.Ser112= (c.336C>T)?

MBD4 p.Ser112= (c.336C>T) is associated with Inborn genetic diseases, tumor predisposition syndrome 2 (ClinVar).

How common is MBD4 p.Ser112= (c.336C>T) in the general population?

MBD4 p.Ser112= (c.336C>T) is rare (popmax 0.132%, nfe) (gnomAD).

MBD4 p.Ser112=

c.336C>T · rs61753468 · VCV2038734

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.132%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.7	GERP 2.1, phastCons 1
Overall
CADD	17.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% European (non-Finnish) · 1,558/1,178,900 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.102% 1,629/1,602,708 alleles · rare exomes 1,535/1,450,398 · genomes 94/152,310 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.132%	757
Remaining individualsnot grpmax-eligible	0.0433%	2,311
Finnishnot grpmax-eligible	0.0385%	2,596
African / African-American	0.028%	3,570
Admixed American	0.00333%	29,986

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: MBD4
Protein: p.Ser112=
Coding: c.336C>T
MANE Select: NM_001276270
dbSNP: rs61753468
Type: single nucleotide variant
Location: chr3:129437308 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.67 · 19 PDB
Residue 112: the mbd domain; a UniProt-annotated variant site (in tpds2; no mbd4 protein detected by immunohistochemical analysis in patient tumor tissue)

Full MBD4 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

Also linked: tumor predisposition syndrome 2

Similar variants

MBD4 p.Ser112Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
MBD4 c.104+1G>A Likely pathogenic ★★ same condition
MBD4 c.1544-1G>A Likely pathogenic ★★ same condition
MBD4 c.1544-1G>T Pathogenic/Likely pathogenic ★★ same condition
MBD4 c.1544-2A>G Likely pathogenic ★★ same condition
MBD4 c.335+1G>A Likely pathogenic ★★ same condition
MBD4 p.Arg181Ter Pathogenic ★★ same condition
MBD4 p.Arg400Ter 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/mbd4-p-ser112 (accessed [today's date]).

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