Is DPM2 p.Val51Ile (c.151G>A) pathogenic?

DPM2 p.Val51Ile (c.151G>A) is classified Uncertain significance in DPM2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-26). AlphaMissense: likely benign (0.0752); Absent from gnomAD v4.1; Associated with congenital muscular dystrophy with intellectual disability and severe epilepsy.

How common is DPM2 p.Val51Ile (c.151G>A) in the general population?

DPM2 p.Val51Ile (c.151G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPM2 p.Val51Ile (c.151G>A)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

DPM2 p.Val51Ile

Q: What condition is associated with DPM2 p.Val51Ile (c.151G>A)?

DPM2 p.Val51Ile (c.151G>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.151G>A · rs1831509385 · VCV1040140

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,552,622)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital muscular dystrophy with intellectual disability and severe epilepsy

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -5.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.038	GERP -2.5, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 2,095 bp · p 0.35 · regional, not allelic
Overall
CADD	5.546	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,552,622). 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.Val51Ile
Coding: c.151G>A
MANE Select: NM_003863
dbSNP: rs1831509385
Type: single nucleotide variant
Location: chr9:127936598 (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.Val51= Likely benign ★ 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 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-val51ile (accessed [today's date]).

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