Is DPM3 p.Arg72His (c.215G>A) pathogenic?

DPM3 p.Arg72His (c.215G>A) is classified Uncertain significance in DPM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-28). AlphaMissense: likely benign (0.0834); Very rare (popmax 0.00167%, amr); Associated with DPM3-congenital disorder of glycosylation.

What condition is associated with DPM3 p.Arg72His (c.215G>A)?

DPM3 p.Arg72His (c.215G>A) is associated with DPM3-congenital disorder of glycosylation (ClinVar).

How common is DPM3 p.Arg72His (c.215G>A) in the general population?

DPM3 p.Arg72His (c.215G>A) is very rare (popmax 0.00167%, amr) (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.Arg72His (c.215G>A)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

DPM3 p.Arg72His

c.215G>A · rs2526668021 · VCV2104655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DPM3-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -10.70	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP -2, phastCons 0.43
Regional constraint	o/e 0.93	unconstrained · MANE · 275 bp · p 0.45 · regional, not allelic
Overall
CADD	18.22	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

Grpmax group 0.00167% Admixed American · 1/60,024 alleles

Overall 6.84e-05% 1/1,461,656 alleles · very 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: DPM3
Protein: p.Arg72His
Coding: c.215G>A
MANE Select: NM_153741
dbSNP: rs2526668021
Type: single nucleotide variant
Location: chr1:155140026 (GRCh38)
Gene constraint: LOEUF 1.364 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.73

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

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-arg72his (accessed [today's date]).

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