Is PGM1 p.Ile83= (c.249C>A) pathogenic?

PGM1 p.Ile83= (c.249C>A) is classified Likely benign in PGM1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-24). Rare (popmax 0.139%, afr); Associated with PGM1-congenital disorder of glycosylation.

What condition is associated with PGM1 p.Ile83= (c.249C>A)?

PGM1 p.Ile83= (c.249C>A) is associated with PGM1-congenital disorder of glycosylation (ClinVar).

How common is PGM1 p.Ile83= (c.249C>A) in the general population?

PGM1 p.Ile83= (c.249C>A) is rare (popmax 0.139%, afr) (gnomAD).

How is PGM1-CDG inherited?

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

PGM1 p.Ile83=

c.249C>A · rs140086116 · VCV1202306

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.139%, afr)

Conditions

PGM1-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.83	acceptor gain · deltas
Pangolin	Δ0.38	gain · loss 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.5	GERP -4.2
Overall
CADD	18.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.139% African / African-American · 104/74,954 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.109%

Overall 0.00676% 109/1,612,866 alleles · rare exomes 41/1,460,650 · genomes 68/152,216 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.139%	721
Remaining individualsnot grpmax-eligible	0.0064%	15,614
Admixed American	0.00167%	60,006

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: PGM1
Protein: p.Ile83=
Coding: c.249C>A
MANE Select: NM_002633
dbSNP: rs140086116
Type: single nucleotide variant
Location: chr1:63629427 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.27 · 16 PDB

Full PGM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PGM1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PGM1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PGM1 p.Ile83Phe Uncertain significance ★ ⚠ same residue
PGM1 p.Arg217Ter Pathogenic ★★ same condition
PGM1 p.Arg293Ter Pathogenic/Likely pathogenic ★★ same condition
PGM1 p.Arg499Ter Pathogenic/Likely pathogenic ★★ same condition
PGM1 p.Arg503Ter Pathogenic ★★ same condition
PGM1 p.Arg515Gln Pathogenic/Likely pathogenic ★★ same condition
PGM1 p.Asp263Tyr Pathogenic/Likely pathogenic ★★ same condition
PGM1 p.Gly291Arg Pathogenic/Likely 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/pgm1-p-ile83 (accessed [today's date]).

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