Is PGM1 p.Phe379= (c.1137C>T) pathogenic?

PGM1 p.Phe379= (c.1137C>T) is classified Likely benign in PGM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-03). Ultra-rare (popmax 0.0521%, afr); Associated with PGM1-congenital disorder of glycosylation.

What condition is associated with PGM1 p.Phe379= (c.1137C>T)?

PGM1 p.Phe379= (c.1137C>T) is associated with PGM1-congenital disorder of glycosylation (ClinVar).

How common is PGM1 p.Phe379= (c.1137C>T) in the general population?

PGM1 p.Phe379= (c.1137C>T) is ultra-rare (popmax 0.0521%, afr) (gnomAD).

How is PGM1-CDG inherited?

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

PGM1 p.Phe379=

c.1137C>T · rs367648776 · VCV518065

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0521%, 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	Δ0.23	donor loss · deltas
Pangolin	Δ0.20	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.69	GERP -3.2, phastCons 0.008
Overall
CADD	10.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0521% African / African-American · 39/74,852 alleles

Filtering AF 0.0391% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0346%

Overall 0.00956% 154/1,610,822 alleles · ultra-rare exomes 118/1,458,678 · genomes 36/152,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0521%	1,919
Admixed American	0.0467%	2,142
Remaining individualsnot grpmax-eligible	0.016%	6,238
South Asian	0.0121%	8,275
East Asian	0.0111%	8,974
European (non-Finnish)	0.0051%	19,619
Finnishnot grpmax-eligible	0.00156%	64,034

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.Phe379=
Coding: c.1137C>T
MANE Select: NM_002633
dbSNP: rs367648776
Type: single nucleotide variant
Location: chr1:63638793 (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 379: a turn

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-phe379 (accessed [today's date]).

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