Is PGM3 p.Tyr488= (c.1464C>T) pathogenic?

PGM3 p.Tyr488= (c.1464C>T) is classified Benign in PGM3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency 23.

What condition is associated with PGM3 p.Tyr488= (c.1464C>T)?

PGM3 p.Tyr488= (c.1464C>T) is associated with immunodeficiency 23 (ClinVar).

How is PGM3-CDG inherited?

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

PGM3 p.Tyr488=

Q: How common is PGM3 p.Tyr488= (c.1464C>T) in the general population?

PGM3 p.Tyr488= (c.1464C>T) is common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1464C>T · rs34873318 · VCV475001

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele

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 2.5	GERP 1, phastCons 1
Overall
CADD	4.487	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.73% African / African-American · 4,296/75,022 alleles

Filtering AF 5.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.52%

Overall 0.329% 5,311/1,614,108 alleles · common exomes 2,746/1,461,836 · genomes 2,565/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.73%	17
Middle Eastern	0.594%	168
Remaining individualsnot grpmax-eligible	0.512%	195
Admixed American	0.498%	201
Ashkenazi Jewishnot grpmax-eligible	0.138%	722
European (non-Finnish)	0.0263%	3,806
South Asian	0.00988%	10,120

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.Tyr488=
Coding: c.1464C>T
MANE Select: NM_015599
dbSNP: rs34873318
Type: single nucleotide variant
Location: chr6:83170380 (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-tyr488 (accessed [today's date]).

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