Is MBD5 p.Ile486= (c.1458T>C) pathogenic?

MBD5 p.Ile486= (c.1458T>C) is classified Likely benign in MBD5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-20). Very rare (popmax 0.00801%, afr); Associated with intellectual disability, autosomal dominant 1.

What condition is associated with MBD5 p.Ile486= (c.1458T>C)?

MBD5 p.Ile486= (c.1458T>C) is associated with intellectual disability, autosomal dominant 1 (ClinVar).

How common is MBD5 p.Ile486= (c.1458T>C) in the general population?

MBD5 p.Ile486= (c.1458T>C) is very rare (popmax 0.00801%, afr) (gnomAD).

MBD5 p.Ile486=

c.1458T>C · rs144232195 · VCV696020

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Conditions

intellectual disability, autosomal dominant 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -1.6, phastCons 1
Overall
CADD	7.199	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,890 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00589% 95/1,613,656 alleles · very rare exomes 84/1,461,574 · genomes 11/152,082 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,808
African / African-Americangrpmax	0.00801%	12,482
European (non-Finnish)	0.00686%	14,567

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile486=
Coding: c.1458T>C
MANE Select: NM_001378120
dbSNP: rs144232195
Type: single nucleotide variant
Location: chr2:148469401 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.20
Residue 486: 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.Ile486Asn Uncertain significance ★ ⚠ 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-ile486 (accessed [today's date]).

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