Is PGM1 p.Pro138= (c.414T>G) pathogenic?

PGM1 p.Pro138= (c.414T>G) is classified Likely benign in PGM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-30). Very rare (popmax 0.00585%, nfe); Associated with PGM1-congenital disorder of glycosylation.

What condition is associated with PGM1 p.Pro138= (c.414T>G)?

PGM1 p.Pro138= (c.414T>G) is associated with PGM1-congenital disorder of glycosylation (ClinVar).

How common is PGM1 p.Pro138= (c.414T>G) in the general population?

PGM1 p.Pro138= (c.414T>G) is very rare (popmax 0.00585%, nfe) (gnomAD).

How is PGM1-CDG inherited?

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

PGM1 p.Pro138=

c.414T>G · rs376259690 · VCV2073951

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00585%, nfe)

Conditions

PGM1-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.15	GERP -3.4, phastCons 0.99
Overall
CADD	8.689	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00585% European (non-Finnish) · 69/1,179,948 alleles

Filtering AF 0.0047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.00434% 70/1,613,966 alleles · very rare exomes 66/1,461,752 · genomes 4/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00585%	17,101
Admixed American	0.00167%	60,004

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.Pro138=
Coding: c.414T>G
MANE Select: NM_002633
dbSNP: rs376259690
Type: single nucleotide variant
Location: chr1:63629946 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.27 · 16 PDB
Residue 138: a β-strand

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.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
PGM1 p.Gly330Arg 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-pro138 (accessed [today's date]).

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