Is DPM1 p.Leu253= (c.759A>G) pathogenic?

DPM1 p.Leu253= (c.759A>G) is classified Conflicting classifications of pathogenicity in DPM1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-03-18). Ultra-rare (popmax 0.0497%, afr); Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Leu253= (c.759A>G)?

DPM1 p.Leu253= (c.759A>G) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Leu253= (c.759A>G) in the general population?

DPM1 p.Leu253= (c.759A>G) is ultra-rare (popmax 0.0497%, afr) (gnomAD).

How is DPM1-CDG inherited?

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

DPM1 p.Leu253=

c.759A>G · rs769964944 · VCV338751

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, afr)

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	0.031	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.9	GERP -2.3, phastCons 1
Overall
CADD	9.151	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0497% African / African-American · 37/74,450 alleles

Filtering AF 0.037% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0327%

Overall 0.00256% 41/1,599,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0497%	2,012
Admixed American	0.00167%	59,930
Remaining individualsnot grpmax-eligible	0.00161%	61,986
European (non-Finnish)	0.000171%	584,051

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.Leu253=
Coding: c.759A>G
dbSNP: rs769964944
Type: single nucleotide variant
Location: chr20:50935156 (GRCh38)

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

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-leu253 (accessed [today's date]).

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