Is PGM3 p.Lys489= (c.1467G>A) pathogenic?

PGM3 p.Lys489= (c.1467G>A) is classified Benign/Likely benign in PGM3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-26). Rare (popmax 0.14%, eas); Associated with immunodeficiency 23.

What condition is associated with PGM3 p.Lys489= (c.1467G>A)?

PGM3 p.Lys489= (c.1467G>A) is associated with immunodeficiency 23 (ClinVar).

How common is PGM3 p.Lys489= (c.1467G>A) in the general population?

PGM3 p.Lys489= (c.1467G>A) is rare (popmax 0.14%, eas) (gnomAD).

How is PGM3-CDG inherited?

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

PGM3 p.Lys489=

c.1467G>A · rs200072483 · VCV760535

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.14%, eas)

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
Pangolin	Δ0.21	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP 0.41	GERP -0.099, phastCons 0.031
Overall
CADD	4.876	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.14% East Asian · 63/44,878 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.00409% 66/1,614,134 alleles · rare exomes 59/1,461,858 · genomes 7/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.14%	712
Remaining individualsnot grpmax-eligible	0.0032%	31,251
African / African-American	0.00133%	75,042

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.Lys489=
Coding: c.1467G>A
MANE Select: NM_015599
dbSNP: rs200072483
Type: single nucleotide variant
Location: chr6:83170377 (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-lys489 (accessed [today's date]).

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