Is MBD5 p.Val769Phe (c.2305G>T) pathogenic?

MBD5 p.Val769Phe (c.2305G>T) is classified Conflicting classifications of pathogenicity in MBD5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-15). AlphaMissense: likely benign (0.1489); Very rare (popmax 0.00769%, sas); Associated with Inborn genetic diseases.

What condition is associated with MBD5 p.Val769Phe (c.2305G>T)?

MBD5 p.Val769Phe (c.2305G>T) is associated with Inborn genetic diseases, intellectual disability, autosomal dominant 1 (ClinVar).

How common is MBD5 p.Val769Phe (c.2305G>T) in the general population?

MBD5 p.Val769Phe (c.2305G>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about MBD5 p.Val769Phe (c.2305G>T)?

AlphaMissense predicts likely benign (score 0.1489) — an in-silico prediction, not a clinical call.

MBD5 p.Val769Phe

c.2305G>T · rs375333284 · VCV3124050

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1489 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1489	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -7.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 27 kb · p 0.0029 · regional, not allelic
Overall
CADD	23.5	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

Grpmax group 0.00769% South Asian · 7/91,084 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000558% 9/1,613,822 alleles · very rare exomes 8/1,461,722 · genomes 1/152,100 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
East Asian	0.00446%	22,443

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: MBD5
Protein: p.Val769Phe
Coding: c.2305G>T
MANE Select: NM_001378120
dbSNP: rs375333284
Type: single nucleotide variant
Location: chr2:148470248 (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

Also linked: intellectual disability, autosomal dominant 1

Similar variants

MBD5 p.Val769Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
MBD5 c.397+1G>A Pathogenic ★★ same condition
MBD5 c.397+2T>C Pathogenic ★★ same condition
MBD5 p.Arg1440Ter Pathogenic ★★ same condition
MBD5 p.Arg200Ter Pathogenic ★★ same condition
MBD5 p.Arg325Ter Pathogenic/Likely pathogenic ★★ same condition
MBD5 p.Cys60Ter Pathogenic ★★ same condition
MBD5 p.Gln587Ter 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/mbd5-p-val769phe (accessed [today's date]).

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