Is MBD4 p.Ser316= (c.948A>G) pathogenic?

MBD4 p.Ser316= (c.948A>G) is classified Benign/Likely benign in MBD4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-10). Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with MBD4 p.Ser316= (c.948A>G)?

MBD4 p.Ser316= (c.948A>G) is associated with Inborn genetic diseases, tumor predisposition syndrome 2 (ClinVar).

How common is MBD4 p.Ser316= (c.948A>G) in the general population?

MBD4 p.Ser316= (c.948A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

MBD4 p.Ser316=

c.948A>G · VCV3640275

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -3.4
Overall
CADD	0.872	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,016 alleles

Overall 6.2e-05% 1/1,614,142 alleles · very rare exomes 1/1,461,832 · genomes 0/152,310 · joint denominator

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.Ser316=
Coding: c.948A>G
MANE Select: NM_001276270
Type: single nucleotide variant
Location: chr3:129436696 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.67 · 19 PDB
Residue 316: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tumor predisposition syndrome 2

Similar variants

MBD4 p.Ser316Pro Uncertain significance ★ ⚠ 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-ser316 (accessed [today's date]).

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