Is DPM2 p.Thr22= (c.66C>A) pathogenic?

DPM2 p.Thr22= (c.66C>A) is classified Likely benign in DPM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-06). Rare (popmax 0.15%, sas); Associated with congenital muscular dystrophy with intellectual disability and severe epilepsy.

How common is DPM2 p.Thr22= (c.66C>A) in the general population?

DPM2 p.Thr22= (c.66C>A) is rare (popmax 0.15%, sas) (gnomAD).

DPM2 p.Thr22=

Q: What condition is associated with DPM2 p.Thr22= (c.66C>A)?

DPM2 p.Thr22= (c.66C>A) 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.66C>A · rs532790675 · VCV1611082

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.15%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -2.8, phastCons 1
Overall
CADD	12.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.15% South Asian · 137/91,078 alleles

Filtering AF 0.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.122%

Overall 0.0088% 142/1,613,856 alleles · rare exomes 137/1,461,648 · genomes 5/152,208 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.15%	665
Remaining individualsnot grpmax-eligible	0.0064%	15,618
East Asian	0.00223%	44,904

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.Thr22=
Coding: c.66C>A
MANE Select: NM_003863
dbSNP: rs532790675
Type: single nucleotide variant
Location: chr9:127937461 (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.Thr22Ala Benign/Likely benign ★★ same residue
DPM2 p.Thr22Ile 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-thr22 (accessed [today's date]).

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