Is DPM2 p.Leu61= (c.183G>A) pathogenic?

DPM2 p.Leu61= (c.183G>A) is classified Benign/Likely benign in DPM2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 19.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with congenital muscular dystrophy with intellectual disability and severe epilepsy.

DPM2 p.Leu61=

Q: What condition is associated with DPM2 p.Leu61= (c.183G>A)?

DPM2 p.Leu61= (c.183G>A) is associated with congenital muscular dystrophy with intellectual disability and severe epilepsy (ClinVar).

Q: How common is DPM2 p.Leu61= (c.183G>A) in the general population?

DPM2 p.Leu61= (c.183G>A) is common (popmax 19.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.183G>A · rs11552794 · VCV128919

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 19.7%, eas) — too common for a highly-penetrant pathogenic allele

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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP -1.4, phastCons 1
Overall
CADD	7.736	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.7% East Asian · 8,563/43,554 alleles

Filtering AF 19.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.2%

Overall 0.978% 15,484/1,583,806 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	19.7%	5
Admixed American	4.53%	22
Finnishnot grpmax-eligible	3.03%	33
Remaining individualsnot grpmax-eligible	1.22%	82
South Asian	0.8%	125
Ashkenazi Jewishnot grpmax-eligible	0.308%	325
Middle Eastern	0.202%	495
African / African-American	0.0757%	1,321
European (non-Finnish)	0.0711%	1,406

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.Leu61=
Coding: c.183G>A
MANE Select: NM_003863
dbSNP: rs11552794
Type: single nucleotide variant
Location: chr9:127936566 (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-p-leu61 (accessed [today's date]).

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