Is PGM1 p.Phe474= (c.1422T>C) pathogenic?

PGM1 p.Phe474= (c.1422T>C) is classified Likely benign in PGM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-04). Ultra-rare (popmax 0.016%, afr); Associated with PGM1-congenital disorder of glycosylation.

What condition is associated with PGM1 p.Phe474= (c.1422T>C)?

PGM1 p.Phe474= (c.1422T>C) is associated with PGM1-congenital disorder of glycosylation (ClinVar).

How common is PGM1 p.Phe474= (c.1422T>C) in the general population?

PGM1 p.Phe474= (c.1422T>C) is ultra-rare (popmax 0.016%, afr) (gnomAD).

How is PGM1-CDG inherited?

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

PGM1 p.Phe474=

c.1422T>C · rs138417403 · VCV2201999

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

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 -0.14	GERP 0.98, phastCons 0.74
Overall
CADD	7.948	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,918 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00112% 18/1,613,936 alleles · ultra-rare exomes 13/1,461,774 · genomes 5/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,243
Remaining individualsnot grpmax-eligible	0.0096%	10,413

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.Phe474=
Coding: c.1422T>C
MANE Select: NM_002633
dbSNP: rs138417403
Type: single nucleotide variant
Location: chr1:63651810 (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.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-phe474 (accessed [today's date]).

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