Is PGM3 p.Ser306= (c.918C>T) pathogenic?

PGM3 p.Ser306= (c.918C>T) is classified Likely benign in PGM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). Very rare (popmax 8.48e-05%, nfe); Associated with immunodeficiency 23.

What condition is associated with PGM3 p.Ser306= (c.918C>T)?

PGM3 p.Ser306= (c.918C>T) is associated with immunodeficiency 23 (ClinVar).

How common is PGM3 p.Ser306= (c.918C>T) in the general population?

PGM3 p.Ser306= (c.918C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is PGM3-CDG inherited?

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

PGM3 p.Ser306=

c.918C>T · rs2128494940 · VCV1622556

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

immunodeficiency 23

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.37	donor loss, 27 bp away · masked 0 · deltas
Pangolin	Δ0.48	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Overall
CADD	6.213	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,312 alleles

Overall 6.2e-05% 1/1,612,764 alleles · very rare exomes 1/1,460,480 · genomes 0/152,284 · 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: PGM3
Protein: p.Ser306=
Coding: c.918C>T
MANE Select: NM_015599
dbSNP: rs2128494940
Type: single nucleotide variant
Location: chr6:83179837 (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-ser306 (accessed [today's date]).

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