Is DPM3 p.Ala43= (c.129C>G) pathogenic?

DPM3 p.Ala43= (c.129C>G) is classified Likely benign in DPM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-17). Very rare (popmax 0.000169%, nfe); Associated with DPM3-congenital disorder of glycosylation.

What condition is associated with DPM3 p.Ala43= (c.129C>G)?

DPM3 p.Ala43= (c.129C>G) is associated with DPM3-congenital disorder of glycosylation (ClinVar).

How common is DPM3 p.Ala43= (c.129C>G) in the general population?

DPM3 p.Ala43= (c.129C>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is DPM3-CDG inherited?

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

DPM3 p.Ala43=

c.129C>G · VCV3639959

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, 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 3.9	GERP -0.31, phastCons 1
Overall
CADD	13.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,036 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,130 alleles · very rare exomes 2/1,461,810 · genomes 0/152,320 · joint denominator

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.Ala43=
Coding: c.129C>G
MANE Select: NM_153741
Type: single nucleotide variant
Location: chr1:155140112 (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.Ala43Thr Uncertain significance ★ ⚠ same residue
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

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-ala43 (accessed [today's date]).

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