Is DPM2 c.*404C>T pathogenic?

DPM2 c.404C>T is classified Uncertain significance in DPM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0164%, sas); Associated with congenital muscular dystrophy with intellectual disability and severe epilepsy.

How common is DPM2 c.*404C>T in the general population?

DPM2 c.*404C>T is ultra-rare (popmax 0.0164%, sas) (gnomAD).

DPM2 c.*404C>T

Q: What condition is associated with DPM2 c.*404C>T?

DPM2 c.*404C>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.

rs1245531633 · VCV915117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, 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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Pangolin	Δ0.23	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -5	GERP -4.4
Non-coding constraint	Z 3.57	1 kb window · o/e 0.76 · regional · uncalibrated
Overall
CADD	6.276	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% South Asian · 5/30,458 alleles

Filtering AF 0.00642% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.00175% 5/286,084 alleles · ultra-rare

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.*404C>T
MANE Select: NM_003863
dbSNP: rs1245531633
Type: single nucleotide variant
Location: chr9:127935318 (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-star-404c-t (accessed [today's date]).

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