Is PGM3 p.Asp128= (c.384T>C) pathogenic?

PGM3 p.Asp128= (c.384T>C) is classified Likely benign in PGM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). Very rare (popmax 0.00134%, afr); Associated with immunodeficiency 23.

What condition is associated with PGM3 p.Asp128= (c.384T>C)?

PGM3 p.Asp128= (c.384T>C) is associated with immunodeficiency 23 (ClinVar).

How common is PGM3 p.Asp128= (c.384T>C) in the general population?

PGM3 p.Asp128= (c.384T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

How is PGM3-CDG inherited?

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

PGM3 p.Asp128=

c.384T>C · rs1170829425 · VCV2898829

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

immunodeficiency 23

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.11	GERP -5, phastCons 0.14
Overall
CADD	4.412	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,792 alleles

Overall 0.000124% 2/1,610,624 alleles · very rare exomes 1/1,458,620 · genomes 1/152,004 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,792
European (non-Finnish)	8.49e-05%	1,177,332

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: PGM3
Protein: p.Asp128=
Coding: c.384T>C
MANE Select: NM_015599
dbSNP: rs1170829425
Type: single nucleotide variant
Location: chr6:83188619 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.54

Full PGM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 23 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PGM3-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

PGM3 c.-2-185C>T Pathogenic/Likely pathogenic ★★ same condition
PGM3 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same condition
PGM3 p.Asn246Ser Pathogenic/Likely pathogenic ★★ same condition
PGM3 p.Gln22Ter Pathogenic/Likely pathogenic ★★ same condition
PGM3 p.Gln262Ter Pathogenic/Likely pathogenic ★★ same condition
PGM3 c.389+6G>A Uncertain significance ★★ same condition
PGM3 c.-2-226T>C Uncertain significance ★★ same condition
PGM3 p.Ala402Thr 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/pgm3-p-asp128 (accessed [today's date]).

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