Is DPM1 p.Pro41= (c.123G>A) pathogenic?

DPM1 p.Pro41= (c.123G>A) is classified Likely benign in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-13). Ultra-rare (popmax 0.0334%, eas); Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Pro41= (c.123G>A)?

DPM1 p.Pro41= (c.123G>A) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Pro41= (c.123G>A) in the general population?

DPM1 p.Pro41= (c.123G>A) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

How is DPM1-CDG inherited?

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

DPM1 p.Pro41=

c.123G>A · rs762396281 · VCV2718570

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Conditions

congenital disorder of glycosylation type 1E

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.098	GERP -3.5, phastCons 0.36
Overall
CADD	11.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,870 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.000991% 16/1,614,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,991
Admixed American	0.00167%	60,032

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: DPM1
Protein: p.Pro41=
Coding: c.123G>A
MANE Select: NM_003859
dbSNP: rs762396281
Type: single nucleotide variant
Location: chr20:50958401 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.61

Full DPM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital disorder of glycosylation type 1E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For DPM1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DPM1 p.Pro41Arg Uncertain significance ★ ⚠ same residue
DPM1 p.Arg92Gly Pathogenic ★★ same condition
DPM1 p.His124Arg Likely pathogenic ★★ same condition
DPM1 p.Met1Leu Pathogenic/Likely pathogenic ★★ same condition
DPM1 c.*12T>C Uncertain significance ★★ same condition
DPM1 p.Ala109Val Uncertain significance ★★ same condition
DPM1 p.Arg12Met Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg191Gln 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/dpm1-p-pro41 (accessed [today's date]).

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