Is DPM2 c.3+6A>G pathogenic?

DPM2 c.3+6A>G is classified Uncertain significance in DPM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). Very rare (popmax 0.00892%, eas); Associated with congenital muscular dystrophy with intellectual disability and severe epilepsy.

How common is DPM2 c.3+6A>G in the general population?

DPM2 c.3+6A>G is very rare (popmax 0.00892%, eas) (gnomAD).

DPM2 c.3+6A>G

Q: What condition is associated with DPM2 c.3+6A>G?

DPM2 c.3+6A>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.

rs776375979 · VCV1399311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

congenital muscular dystrophy with intellectual disability and severe epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +6	donor splice region (+6, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	Δ0.50	donor gain · deltas
Pangolin	Δ0.35	gain · loss 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.64	GERP -3.4, phastCons 0.63
Overall
CADD	9.827	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,856 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00346%

Overall 0.00386% 62/1,607,744 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,214
European (non-Finnish)	0.00484%	20,647
Remaining individualsnot grpmax-eligible	0.00161%	62,224

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+6A>G
MANE Select: NM_003863
dbSNP: rs776375979
Type: single nucleotide variant
Location: chr9:127937812 (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.3+12A>G Benign/Likely benign ★★ same condition
DPM2 c.94-8G>T Likely 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-6a-g (accessed [today's date]).

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