Is DPM2 p.Arg47Ter (c.139C>T) pathogenic?

DPM2 p.Arg47Ter (c.139C>T) is classified Pathogenic/Likely pathogenic in DPM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-25). Very rare (popmax 0.00127%, sas); Associated with congenital muscular dystrophy with intellectual disability and severe epilepsy.

How common is DPM2 p.Arg47Ter (c.139C>T) in the general population?

DPM2 p.Arg47Ter (c.139C>T) is very rare (popmax 0.00127%, sas) (gnomAD).

DPM2 p.Arg47Ter

Q: What condition is associated with DPM2 p.Arg47Ter (c.139C>T)?

DPM2 p.Arg47Ter (c.139C>T) 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.

c.139C>T · rs549450795 · VCV1065328

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00127%, sas)

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.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.7	GERP 1.2, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% South Asian · 1/78,904 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000291% 4/1,376,268 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00127%	78,904
European (non-Finnish)	0.000264%	378,815

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
Protein: p.Arg47Ter
Coding: c.139C>T
MANE Select: NM_003863
dbSNP: rs549450795
Type: single nucleotide variant
Location: chr9:127936610 (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.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
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-p-arg47ter (accessed [today's date]).

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