Is MBD4 p.Phe207Ser (c.620T>C) pathogenic?

MBD4 p.Phe207Ser (c.620T>C) is classified Uncertain significance in MBD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely benign (0.0685); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with MBD4 p.Phe207Ser (c.620T>C)?

MBD4 p.Phe207Ser (c.620T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MBD4 p.Phe207Ser (c.620T>C) in the general population?

MBD4 p.Phe207Ser (c.620T>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about MBD4 p.Phe207Ser (c.620T>C)?

AlphaMissense predicts likely benign (score 0.0685) — an in-silico prediction, not a clinical call.

MBD4 p.Phe207Ser

c.620T>C · rs773333749 · VCV2620150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0685 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0685	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -3.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.57	GERP -4.3
Regional constraint	o/e 0.92	unconstrained · MANE · 8,329 bp · p 0.034 · regional, not allelic
Overall
CADD	3.505	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,614,174 alleles · very rare exomes 2/1,461,880 · genomes 0/152,294 · 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.Phe207Ser
Coding: c.620T>C
MANE Select: NM_001276270
dbSNP: rs773333749
Type: single nucleotide variant
Location: chr3:129437024 (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.Phe207= Likely benign ★★ same residue
MBD4 p.Phe207Ile Uncertain significance ★ ⚠ same residue
MBD4 p.Phe207Leu Conflicting classifications of pathogenicity ★ ⚠ 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-phe207ser (accessed [today's date]).

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