Is MBD5 p.Asp57= (c.171T>C) pathogenic?

MBD5 p.Asp57= (c.171T>C) is classified Likely benign in MBD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-27). Very rare (popmax 0.00134%, afr); Associated with intellectual disability, autosomal dominant 1.

What condition is associated with MBD5 p.Asp57= (c.171T>C)?

MBD5 p.Asp57= (c.171T>C) is associated with intellectual disability, autosomal dominant 1 (ClinVar).

How common is MBD5 p.Asp57= (c.171T>C) in the general population?

MBD5 p.Asp57= (c.171T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

MBD5 p.Asp57=

c.171T>C · rs1707126434 · VCV1095895

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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	<0.2	all four deltas below 0.2 · T>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.71	GERP -1.5, phastCons 0.015
Overall
CADD	7.531	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,892 alleles

Overall 6.2e-05% 1/1,613,104 alleles · very rare exomes 0/1,460,930 · genomes 1/152,174 · 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.Asp57=
Coding: c.171T>C
MANE Select: NM_001378120
dbSNP: rs1707126434
Type: single nucleotide variant
Location: chr2:148462639 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.20
Residue 57: the mbd domain; the 'required for interaction with asxl1/2/3' 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 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
MBD5 p.Gln813Ter Pathogenic/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/mbd5-p-asp57 (accessed [today's date]).

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