Is PGM3 p.Val76fs (c.226del) pathogenic?

PGM3 p.Val76fs (c.226del) is classified Pathogenic in PGM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). No gnomAD frequency available for this variant; Associated with immunodeficiency 23.

What condition is associated with PGM3 p.Val76fs (c.226del)?

PGM3 p.Val76fs (c.226del) is associated with immunodeficiency 23 (ClinVar).

How common is PGM3 p.Val76fs (c.226del) in the general population?

PGM3 p.Val76fs (c.226del) is no gnomAD frequency available for this variant (gnomAD).

How is PGM3-CDG inherited?

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

PGM3 p.Val76fs

c.226del · rs2538211894 · VCV3000165

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

immunodeficiency 23

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 2.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PGM3
Protein: p.Val76fs
Coding: c.226del
MANE Select: NM_015599
dbSNP: rs2538211894
Type: Deletion
Location: chr6:83188777 (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 p.Leu452fs Pathogenic ★★ same condition
PGM3 p.Lys54fs Pathogenic ★★ same condition
PGM3 p.Met385fs Pathogenic/Likely pathogenic ★★ same condition
PGM3 p.Ser133fs Pathogenic ★★ same condition
PGM3 c.390-232_417del Likely pathogenic ★ same condition
PGM3 c.-2-238del Pathogenic ★ same condition
PGM3 c.-2-242_-2-241del Pathogenic ★ same condition
PGM3 p.Arg127fs Pathogenic ★ 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-val76fs (accessed [today's date]).

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