Is PGM3 p.Arg459= (c.1377G>A) pathogenic?

PGM3 p.Arg459= (c.1377G>A) is classified Likely benign in PGM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-18). Very rare (popmax 0.000254%, nfe); Associated with immunodeficiency 23.

What condition is associated with PGM3 p.Arg459= (c.1377G>A)?

PGM3 p.Arg459= (c.1377G>A) is associated with immunodeficiency 23 (ClinVar).

How common is PGM3 p.Arg459= (c.1377G>A) in the general population?

PGM3 p.Arg459= (c.1377G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is PGM3-CDG inherited?

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

PGM3 p.Arg459=

c.1377G>A · rs1386270701 · VCV2867318

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

immunodeficiency 23

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.25	GERP -2.2, phastCons 0.98
Overall
CADD	6.193	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,818 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,770 alleles · very rare exomes 2/1,461,596 · genomes 2/152,174 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,468
European (non-Finnish)grpmax	0.000254%	393,272

Remaining individuals 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: PGM3
Protein: p.Arg459=
Coding: c.1377G>A
MANE Select: NM_015599
dbSNP: rs1386270701
Type: single nucleotide variant
Location: chr6:83170467 (GRCh38)

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

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-arg459 (accessed [today's date]).

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