Is DPM3 p.Pro42Ala (c.124C>G) pathogenic?

DPM3 p.Pro42Ala (c.124C>G) is classified Pathogenic/Likely pathogenic in DPM3 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2020-08-25). AlphaMissense: ambiguous (0.4311); Absent from gnomAD v4.1; Associated with DPM3-congenital disorder of glycosylation.

What condition is associated with DPM3 p.Pro42Ala (c.124C>G)?

DPM3 p.Pro42Ala (c.124C>G) is associated with DPM3-congenital disorder of glycosylation, muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15 (ClinVar).

How common is DPM3 p.Pro42Ala (c.124C>G) in the general population?

DPM3 p.Pro42Ala (c.124C>G) is absent from gnomAD v4.1 (gnomAD).

How is DPM3-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DPM3 p.Pro42Ala (c.124C>G)?

AlphaMissense predicts ambiguous (score 0.4311) — an in-silico prediction, not a clinical call.

DPM3 p.Pro42Ala

c.124C>G · rs745692004 · VCV694292

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4311 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

DPM3-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.4311	ambiguous
REVEL	0.931	moderately pathogenic-leaning
SaProt	LLR -12.34	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 275 bp · p 0.45 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPM3
Protein: p.Pro42Ala
Coding: c.124C>G
MANE Select: NM_153741
dbSNP: rs745692004
Type: single nucleotide variant
Location: chr1:155140117 (GRCh38)
Gene constraint: LOEUF 1.364 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.73
Residue 42: a UniProt-annotated variant site (in mddgb15; uncertain significance)

Full DPM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DPM3-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15

For DPM3-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

DPM3 p.Ala70Thr Uncertain significance ★★ ⚠ same condition
DPM3 p.Ala86Asp Uncertain significance ★★ ⚠ same condition
DPM3 p.Arg60Cys Uncertain significance ★★ ⚠ same condition
DPM3 p.Arg60Leu Uncertain significance ★★ ⚠ same condition
DPM3 p.Glu73Ala Uncertain significance ★★ ⚠ same condition
DPM3 p.Gly89Glu Uncertain significance ★★ ⚠ same condition
DPM3 p.Trp7Arg Uncertain significance ★★ ⚠ same condition
DPM3 p.Tyr59Ser 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/dpm3-p-pro42ala (accessed [today's date]).

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