Is MBD5 p.Pro342del (c.1017TCC[1]) pathogenic?

MBD5 p.Pro342del (c.1017TCC[1]) is classified Uncertain significance in MBD5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-08-31). Very rare (popmax 0.00017%, nfe); Associated with intellectual disability, autosomal dominant 1.

What condition is associated with MBD5 p.Pro342del (c.1017TCC[1])?

MBD5 p.Pro342del (c.1017TCC[1]) is associated with intellectual disability, autosomal dominant 1 (ClinVar).

How common is MBD5 p.Pro342del (c.1017TCC[1]) in the general population?

MBD5 p.Pro342del (c.1017TCC[1]) is very rare (popmax 0.00017%, nfe) (gnomAD).

MBD5 p.Pro342del

c.1017TCC[1] · rs1388983985 · VCV835318

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

intellectual disability, autosomal dominant 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,908 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,810 alleles · very rare exomes 2/1,461,584 · genomes 0/152,226 · 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: MBD5
Protein: p.Pro342del
Coding: c.1017TCC[1]
MANE Select: NM_001378120
dbSNP: rs1388983985
Type: Microsatellite
Location: chr2:148468958 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.20
Residue 342: the 'disordered' region

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.Pro342His Uncertain significance ★★ ⚠ same residue
MBD5 p.Pro342Thr Pathogenic same residue
MBD5 p.Arg252del Uncertain significance ★★ same condition
MBD5 p.Ile297fs Pathogenic ★ same condition
MBD5 p.Ser1166fs Likely pathogenic ★ same condition
MBD5 p.Gln192del Uncertain significance ★ same condition
MBD5 p.Met474del Uncertain significance ★ same condition
MBD5 p.Thr862del 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-pro342del (accessed [today's date]).

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