Is DPM2 p.Ala56Phe (c.166_167delinsTT) pathogenic?

DPM2 p.Ala56Phe (c.166167delinsTT) is classified Uncertain significance in DPM2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-01-02). Absent from gnomAD; Associated with congenital muscular dystrophy with intellectual disability and severe epilepsy.

What condition is associated with DPM2 p.Ala56Phe (c.166_167delinsTT)?

DPM2 p.Ala56Phe (c.166_167delinsTT) is associated with congenital muscular dystrophy with intellectual disability and severe epilepsy (ClinVar).

How common is DPM2 p.Ala56Phe (c.166_167delinsTT) in the general population?

DPM2 p.Ala56Phe (c.166_167delinsTT) is absent from gnomAD (gnomAD).

DPM2 p.Ala56Phe

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.166_167delinsTT · rs2131648142 · VCV1701582

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 0.7	GERP 0.14, phastCons 0.09
Regional constraint	o/e 0.91	unconstrained · MANE · 2,095 bp · p 0.35 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DPM2
Protein: p.Ala56Phe
Coding: c.166_167delinsTT
MANE Select: NM_003863
dbSNP: rs2131648142
Type: Indel
Location: chr9:127936582 (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.Ala56Ser Uncertain significance ★ ⚠ same residue
DPM2 p.Ala56Val Uncertain significance ★ ⚠ same residue
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

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-ala56phe (accessed [today's date]).

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