Is MBD4 p.Ser58= (c.174C>T) pathogenic?

MBD4 p.Ser58= (c.174C>T) is classified Likely benign in MBD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). Very rare (popmax 0.00223%, eas).

How common is MBD4 p.Ser58= (c.174C>T) in the general population?

MBD4 p.Ser58= (c.174C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

MBD4 p.Ser58=

c.174C>T · VCV3665597

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 3	GERP -0.1, phastCons 0.82
Overall
CADD	7.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,864 alleles

Overall 6.2e-05% 1/1,613,848 alleles · very rare exomes 1/1,461,718 · genomes 0/152,130 · 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.Ser58=
Coding: c.174C>T
MANE Select: NM_001276270
Type: single nucleotide variant
Location: chr3:129437881 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.67 · 19 PDB

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

Similar variants

MBD4 p.Ser58Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
MBD4 p.Ser58Asn Uncertain significance ★ ⚠ same residue
MBD4 c.104+1G>A Likely pathogenic ★★ same type
MBD4 c.1544-1G>A Likely pathogenic ★★ same type
MBD4 c.1544-1G>T Pathogenic/Likely pathogenic ★★ same type
MBD4 c.1544-2A>G Likely pathogenic ★★ same type
MBD4 c.335+1G>A Likely pathogenic ★★ same type
MBD4 p.Arg181Ter Pathogenic ★★ same type

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-ser58 (accessed [today's date]).

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