Is PGM1 p.Ser247= (c.741G>C) pathogenic?

PGM1 p.Ser247= (c.741G>C) is classified Likely benign in PGM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-03). Ultra-rare (popmax 0.0137%, eas); Associated with PGM1-congenital disorder of glycosylation.

What condition is associated with PGM1 p.Ser247= (c.741G>C)?

PGM1 p.Ser247= (c.741G>C) is associated with PGM1-congenital disorder of glycosylation (ClinVar).

How common is PGM1 p.Ser247= (c.741G>C) in the general population?

PGM1 p.Ser247= (c.741G>C) is ultra-rare (popmax 0.0137%, eas) (gnomAD).

How is PGM1-CDG inherited?

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

PGM1 p.Ser247=

c.741G>C · rs142222746 · VCV1099405

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, eas)

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 -8.6	GERP -4.2
Overall
CADD	0.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0137% East Asian · 6/43,672 alleles

Filtering AF 0.00592% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00403%

Overall 0.000506% 8/1,579,756 alleles · ultra-rare exomes 6/1,453,528 · genomes 2/126,228 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0137%	7,279
Remaining individualsnot grpmax-eligible	0.00162%	61,554
European (non-Finnish)	8.59e-05%	1,164,308

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.Ser247=
Coding: c.741G>C
MANE Select: NM_002633
dbSNP: rs142222746
Type: single nucleotide variant
Location: chr1:63634887 (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 247: an α-helix

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-ser247 (accessed [today's date]).

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