Is PGM1 p.Arg329His (c.986G>A) pathogenic?

PGM1 p.Arg329His (c.986G>A) is classified Uncertain significance in PGM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.0961); Very rare (popmax 0.00534%, afr); Associated with PGM1-congenital disorder of glycosylation.

What condition is associated with PGM1 p.Arg329His (c.986G>A)?

PGM1 p.Arg329His (c.986G>A) is associated with PGM1-congenital disorder of glycosylation (ClinVar).

How common is PGM1 p.Arg329His (c.986G>A) in the general population?

PGM1 p.Arg329His (c.986G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

How is PGM1-CDG inherited?

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

What do computational predictors say about PGM1 p.Arg329His (c.986G>A)?

AlphaMissense predicts likely benign (score 0.0961) — an in-silico prediction, not a clinical call.

PGM1 p.Arg329His

c.986G>A · rs747394265 · VCV1417469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PGM1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0961	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -7.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP -2.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 23 kb · p 0.87 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,926 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000929% 15/1,613,990 alleles · very rare exomes 13/1,461,830 · genomes 2/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,732
Admixed American	0.00333%	29,999
South Asian	0.0022%	45,546
Remaining individualsnot grpmax-eligible	0.0016%	62,474
European (non-Finnish)	0.000508%	196,667

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.Arg329His
Coding: c.986G>A
MANE Select: NM_002633
dbSNP: rs747394265
Type: single nucleotide variant
Location: chr1:63636346 (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.Arg329Cys Uncertain significance ★★ ⚠ same residue
PGM1 p.Arg329= Benign/Likely benign ★★ same residue
PGM1 p.Arg329Leu Uncertain significance ★ ⚠ same residue
PGM1 p.Arg329Ser 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

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-arg329his (accessed [today's date]).

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