Is DPM2 p.Gln37fs (c.108_111del) pathogenic?

DPM2 p.Gln37fs (c.108111del) is classified Uncertain significance in DPM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-13). Very rare (popmax 0.00238%, eas); Associated with congenital muscular dystrophy with intellectual disability and severe epilepsy.

What condition is associated with DPM2 p.Gln37fs (c.108_111del)?

DPM2 p.Gln37fs (c.108_111del) is associated with congenital muscular dystrophy with intellectual disability and severe epilepsy (ClinVar).

How common is DPM2 p.Gln37fs (c.108_111del) in the general population?

DPM2 p.Gln37fs (c.108_111del) is very rare (popmax 0.00238%, eas) (gnomAD).

DPM2 p.Gln37fs

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.108_111del · rs756881158 · VCV1006598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00238%, 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 carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Overall
CADD	35.0	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 0.00238% East Asian · 1/41,964 alleles

Filtering AF 0.00108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00087%

Overall 0.00133% 20/1,505,462 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00238%	41,964
European (non-Finnish)	0.00169%	59,263

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.Gln37fs
Coding: c.108_111del
MANE Select: NM_003863
dbSNP: rs756881158
Type: Deletion
Location: chr9:127936638 (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.Gln37Ter Pathogenic ★ same residue
DPM2 p.Gly10fs Pathogenic ★ same condition
DPM2 p.Leu13fs Pathogenic ★ same condition
DPM2 c.94-14del Likely benign ★ same condition
DPM2 p.Arg47Ter Pathogenic/Likely pathogenic ★★ same condition
DPM2 p.Ala52Thr Uncertain significance ★★ ⚠ same condition
DPM2 p.Ala56Phe Uncertain significance ★★ same condition
DPM2 p.Leu30Val Uncertain significance ★★ ⚠ 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-gln37fs (accessed [today's date]).

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