Is MBD2 p.Ala172Val (c.515C>T) pathogenic?

MBD2 p.Ala172Val (c.515C>T) is classified Uncertain significance in MBD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.9963); Very rare (popmax 0.00137%, afr).

How common is MBD2 p.Ala172Val (c.515C>T) in the general population?

MBD2 p.Ala172Val (c.515C>T) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about MBD2 p.Ala172Val (c.515C>T)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

MBD2 p.Ala172Val

c.515C>T · VCV4104578

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic
REVEL	0.878	moderately pathogenic-leaning
SaProt	LLR -9.94	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 64 kb · p 4.1e-10 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% African / African-American · 1/73,204 alleles

Overall 0.000126% 2/1,581,552 alleles · very rare exomes 1/1,432,392 · genomes 1/149,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	73,204
South Asian	0.00111%	90,452

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: MBD2
Protein: p.Ala172Val
Coding: c.515C>T
MANE Select: NM_003927
Type: single nucleotide variant
Location: chr18:54224045 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 68.37 · 14 PDB
Residue 172: the mbd domain; a turn

Full MBD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MBD2 p.Pro348= Benign ★★ same type
MBD2 p.Arg394Gln Uncertain significance ★ ⚠ same type
MBD2 p.Arg86Leu Uncertain significance ★ ⚠ same type
MBD2 p.Arg90Pro Uncertain significance ★ ⚠ same type
MBD2 p.Arg92Gly Uncertain significance ★ ⚠ same type
MBD2 p.Arg94Cys Uncertain significance ★ same type
MBD2 p.Asp107Asn Uncertain significance ★ ⚠ same type
MBD2 p.Gln66Glu Uncertain significance ★ ⚠ same type

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/mbd2-p-ala172val (accessed [today's date]).

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