Is DPM3 p.Leu38= (c.112C>T) pathogenic?

DPM3 p.Leu38= (c.112C>T) is classified Benign in DPM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-09). Very rare (popmax 0.00297%, nfe); Associated with DPM3-congenital disorder of glycosylation.

What condition is associated with DPM3 p.Leu38= (c.112C>T)?

DPM3 p.Leu38= (c.112C>T) is associated with DPM3-congenital disorder of glycosylation (ClinVar).

How common is DPM3 p.Leu38= (c.112C>T) in the general population?

DPM3 p.Leu38= (c.112C>T) is very rare (popmax 0.00297%, nfe) (gnomAD).

How is DPM3-CDG inherited?

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

DPM3 p.Leu38=

c.112C>T · rs368529799 · VCV1167448

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Conditions

DPM3-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.32, phastCons 1
Overall
CADD	12.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% European (non-Finnish) · 35/1,180,048 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.011% 178/1,614,036 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.22%	454
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)grpmax	0.00297%	33,716

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu38=
Coding: c.112C>T
MANE Select: NM_153741
dbSNP: rs368529799
Type: single nucleotide variant
Location: chr1:155140129 (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-leu38 (accessed [today's date]).

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