Is DPM2 c.3+12A>G pathogenic?

DPM2 c.3+12A>G is classified Benign/Likely benign in DPM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). Rare (popmax 0.858%, afr); Associated with congenital muscular dystrophy with intellectual disability and severe epilepsy.

How common is DPM2 c.3+12A>G in the general population?

DPM2 c.3+12A>G is rare (popmax 0.858%, afr) (gnomAD).

DPM2 c.3+12A>G

Q: What condition is associated with DPM2 c.3+12A>G?

DPM2 c.3+12A>G is associated with congenital muscular dystrophy with intellectual disability and severe epilepsy (ClinVar).

Q: How is Congenital muscular dystrophy with intellectual disability and severe epilepsy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

rs2274425 · VCV508270

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.858%, afr)

Conditions

congenital muscular dystrophy with intellectual disability and severe epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +12	near-intronic (+12 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.005	GERP -2.5
Overall
CADD	0.493	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.858% African / African-American · 642/74,858 alleles

Filtering AF 0.803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.781%

Overall 0.0508% 818/1,609,336 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.858%	117
Middle Eastern	0.431%	232
East Asian	0.165%	606
Remaining individualsnot grpmax-eligible	0.0498%	2,009
Admixed American	0.0455%	2,200
South Asian	0.00221%	45,218
European (non-Finnish)	0.00136%	73,604

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: DPM2
Coding: c.3+12A>G
MANE Select: NM_003863
dbSNP: rs2274425
Type: single nucleotide variant
Location: chr9:127937806 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.96

Full DPM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital muscular dystrophy with intellectual disability and severe epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital muscular dystrophy with intellectual disability and severe epilepsy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DPM2 p.Arg47Ter Pathogenic/Likely pathogenic ★★ same condition
DPM2 p.Ala52Thr Uncertain significance ★★ ⚠ same condition
DPM2 p.Leu30Val Uncertain significance ★★ ⚠ same condition
DPM2 p.Leu62Val Uncertain significance ★★ ⚠ same condition
DPM2 p.Tyr43His Uncertain significance ★★ ⚠ same condition
DPM2 p.Val51Ile Uncertain significance ★★ ⚠ same condition
DPM2 c.94-8G>T Likely benign ★★ same condition
DPM2 c.-152A>G Benign ★★ 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/dpm2-c-3-plus-12a-g (accessed [today's date]).

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