Is MBD5 p.Ser925Phe (c.2774C>T) pathogenic?

MBD5 p.Ser925Phe (c.2774C>T) is classified Uncertain significance in MBD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: ambiguous (0.5263); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MBD5 p.Ser925Phe (c.2774C>T)?

MBD5 p.Ser925Phe (c.2774C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MBD5 p.Ser925Phe (c.2774C>T) in the general population?

MBD5 p.Ser925Phe (c.2774C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MBD5 p.Ser925Phe (c.2774C>T)?

AlphaMissense predicts ambiguous (score 0.5263) — an in-silico prediction, not a clinical call.

MBD5 p.Ser925Phe

c.2774C>T · VCV4104702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5263 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5263	ambiguous
REVEL	0.301	indeterminate
SaProt	LLR -9.37	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 27 kb · p 0.0029 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MBD5
Protein: p.Ser925Phe
Coding: c.2774C>T
MANE Select: NM_001378120
Type: single nucleotide variant
Location: chr2:148483365 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.20

Full MBD5 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

MBD5 p.Ser925Thr Uncertain significance ★ ⚠ same residue
MBD5 p.Ala1244Asp Uncertain significance ★★ ⚠ same condition
MBD5 p.Ala851Glu Uncertain significance ★★ ⚠ same condition
MBD5 p.Arg1395Thr Uncertain significance ★★ same condition
MBD5 p.Arg1398Trp Uncertain significance ★★ ⚠ same condition
MBD5 p.Asn418Tyr Uncertain significance ★★ ⚠ same condition
MBD5 p.Asp1572His Uncertain significance ★★ ⚠ same condition
MBD5 p.Glu1416Lys Uncertain significance ★★ 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/mbd5-p-ser925phe (accessed [today's date]).

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