Is MBD4 p.Phe207= (c.621T>C) pathogenic?

MBD4 p.Phe207= (c.621T>C) is classified Likely benign in MBD4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with MBD4 p.Phe207= (c.621T>C)?

MBD4 p.Phe207= (c.621T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MBD4 p.Phe207= (c.621T>C) in the general population?

MBD4 p.Phe207= (c.621T>C) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

MBD4 p.Phe207=

c.621T>C · VCV3630786

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.35	GERP -3.3
Overall
CADD	2.295	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,888 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.000619% 10/1,614,230 alleles · ultra-rare exomes 10/1,461,880 · genomes 0/152,350 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,413
Remaining individualsnot grpmax-eligible	0.0048%	20,836

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.Phe207=
Coding: c.621T>C
MANE Select: NM_001276270
Type: single nucleotide variant
Location: chr3:129437023 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.67 · 19 PDB
Residue 207: 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)

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

Similar variants

MBD4 p.Phe207Ile Uncertain significance ★ ⚠ same residue
MBD4 p.Phe207Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MBD4 p.Phe207Ser Uncertain significance ★ ⚠ same residue
MBD4 p.Phe207Thr Uncertain significance ★★ same residue
MBD4 p.Phe207fs Pathogenic ★ same residue
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

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-phe207 (accessed [today's date]).

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