Is MBD5 p.Pro167fs (c.498_499insTA) pathogenic?

MBD5 p.Pro167fs (c.498499insTA) is classified Likely pathogenic in MBD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-07-31). Associated with intellectual disability, autosomal dominant 1.

What condition is associated with MBD5 p.Pro167fs (c.498_499insTA)?

MBD5 p.Pro167fs (c.498_499insTA) is associated with intellectual disability, autosomal dominant 1 (ClinVar).

MBD5 p.Pro167fs

c.498_499insTA · VCV4886902

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual disability, autosomal dominant 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP 1.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: MBD5
Protein: p.Pro167fs
Coding: c.498_499insTA
MANE Select: NM_001378120
Type: Insertion
Location: chr2:148468441 (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

intellectual disability, autosomal dominant 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MBD5 p.Arg494fs Likely pathogenic ★ same condition
MBD5 p.Lys1589fs Pathogenic ★ same condition
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

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-pro167fs (accessed [today's date]).

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