Is DPM1 p.Leu4= (c.10T>C) pathogenic?

DPM1 p.Leu4= (c.10T>C) is classified Likely benign in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-28). Ultra-rare (popmax 0.0268%, afr); Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Leu4= (c.10T>C)?

DPM1 p.Leu4= (c.10T>C) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Leu4= (c.10T>C) in the general population?

DPM1 p.Leu4= (c.10T>C) is ultra-rare (popmax 0.0268%, afr) (gnomAD).

How is DPM1-CDG inherited?

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

DPM1 p.Leu4=

c.10T>C · rs373612327 · VCV2063790

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, 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	0.022	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -3.1
Overall
CADD	2.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0268% African / African-American · 20/74,740 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00155% 25/1,613,378 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0268%	3,737
Admixed American	0.005%	19,987
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Leu4=
Coding: c.10T>C
MANE Select: NM_003859
dbSNP: rs373612327
Type: single nucleotide variant
Location: chr20:50958514 (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.Leu4Trp Uncertain significance ★ ⚠ same residue
DPM1 p.Leu4Phe 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

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-leu4 (accessed [today's date]).

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