Is PGM1 p.Pro140= (c.420A>G) pathogenic?

PGM1 p.Pro140= (c.420A>G) is classified Likely benign in PGM1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-23). Ultra-rare (popmax 0.0366%, nfe); Associated with PGM1-congenital disorder of glycosylation.

What condition is associated with PGM1 p.Pro140= (c.420A>G)?

PGM1 p.Pro140= (c.420A>G) is associated with PGM1-congenital disorder of glycosylation (ClinVar).

How common is PGM1 p.Pro140= (c.420A>G) in the general population?

PGM1 p.Pro140= (c.420A>G) is ultra-rare (popmax 0.0366%, nfe) (gnomAD).

How is PGM1-CDG inherited?

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

PGM1 p.Pro140=

c.420A>G · rs141007881 · VCV297873

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0366%, 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 -2.4	GERP -4.2
Overall
CADD	5.457	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0366% European (non-Finnish) · 432/1,179,972 alleles

Filtering AF 0.0337% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0326%

Overall 0.0304% 490/1,613,994 alleles · ultra-rare exomes 456/1,461,772 · genomes 34/152,222 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0384%	2,603
European (non-Finnish)grpmax	0.0366%	2,731
South Asian	0.0296%	3,374
African / African-American	0.00534%	18,730
Finnishnot grpmax-eligible	0.00312%	32,020
Admixed American	0.00167%	60,008

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro140=
Coding: c.420A>G
MANE Select: NM_002633
dbSNP: rs141007881
Type: single nucleotide variant
Location: chr1:63629952 (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

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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-pro140 (accessed [today's date]).

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