Is MBD5 p.Pro196= (c.588T>C) pathogenic?

MBD5 p.Pro196= (c.588T>C) is classified Likely benign in MBD5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-01). Very rare (popmax 0.00636%, nfe); Associated with intellectual disability, autosomal dominant 1.

What condition is associated with MBD5 p.Pro196= (c.588T>C)?

MBD5 p.Pro196= (c.588T>C) is associated with intellectual disability, autosomal dominant 1 (ClinVar).

How common is MBD5 p.Pro196= (c.588T>C) in the general population?

MBD5 p.Pro196= (c.588T>C) is very rare (popmax 0.00636%, nfe) (gnomAD).

MBD5 p.Pro196=

c.588T>C · rs373675091 · VCV385747

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00636%, 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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.037	GERP -4.8, phastCons 0.9
Overall
CADD	7.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00636% European (non-Finnish) · 75/1,179,896 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00477% 77/1,613,806 alleles · very rare exomes 75/1,461,684 · genomes 2/152,122 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00636%	15,732
Remaining individualsnot grpmax-eligible	0.0032%	31,237

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.Pro196=
Coding: c.588T>C
MANE Select: NM_001378120
dbSNP: rs373675091
Type: single nucleotide variant
Location: chr2:148468531 (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 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-pro196 (accessed [today's date]).

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