Is MBD5 p.Pro272Ser (c.814C>T) pathogenic?

MBD5 p.Pro272Ser (c.814C>T) is classified Uncertain significance in MBD5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-31). AlphaMissense: likely benign (0.2435); Very rare (popmax 0.00133%, afr); Associated with intellectual disability, autosomal dominant 1.

What condition is associated with MBD5 p.Pro272Ser (c.814C>T)?

MBD5 p.Pro272Ser (c.814C>T) is associated with intellectual disability, autosomal dominant 1 (ClinVar).

How common is MBD5 p.Pro272Ser (c.814C>T) in the general population?

MBD5 p.Pro272Ser (c.814C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about MBD5 p.Pro272Ser (c.814C>T)?

AlphaMissense predicts likely benign (score 0.2435) — an in-silico prediction, not a clinical call.

MBD5 p.Pro272Ser

c.814C>T · rs2469858013 · VCV1803492

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2435 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

intellectual disability, autosomal dominant 1

Computational evidence

Protein change
AlphaMissense	0.2435	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -6.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 27 kb · p 0.0029 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,994 alleles

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

Overall 0.000186% 3/1,613,934 alleles · very rare exomes 3/1,461,724 · genomes 0/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,994
European (non-Finnish)	0.00017%	589,950

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.Pro272Ser
Coding: c.814C>T
MANE Select: NM_001378120
dbSNP: rs2469858013
Type: single nucleotide variant
Location: chr2:148468757 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.20
Residue 272: 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.Pro272Arg 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-pro272ser (accessed [today's date]).

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