Is PGM1 p.Phe148Val (c.442T>G) pathogenic?

PGM1 p.Phe148Val (c.442T>G) is classified Conflicting classifications of pathogenicity in PGM1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-28). AlphaMissense: likely pathogenic (0.8401); Rare (popmax 0.158%, amr); Associated with PGM1-congenital disorder of glycosylation.

What condition is associated with PGM1 p.Phe148Val (c.442T>G)?

PGM1 p.Phe148Val (c.442T>G) is associated with PGM1-congenital disorder of glycosylation (ClinVar).

How common is PGM1 p.Phe148Val (c.442T>G) in the general population?

PGM1 p.Phe148Val (c.442T>G) is rare (popmax 0.158%, amr) (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.Phe148Val (c.442T>G)?

AlphaMissense predicts likely pathogenic (score 0.8401) — an in-silico prediction, not a clinical call.

PGM1 p.Phe148Val

c.442T>G · rs755467080 · VCV740598

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8401 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.158%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

PGM1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.8401	likely pathogenic
REVEL	0.588	indeterminate
SaProt	LLR -11.04	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 41 kb · p 0.25 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.158% Admixed American · 95/59,994 alleles

Filtering AF 0.133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00644% 104/1,613,938 alleles · rare exomes 95/1,461,774 · genomes 9/152,164 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.158%	632
Remaining individualsnot grpmax-eligible	0.0112%	8,926
European (non-Finnish)	0.000169%	589,984

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.Phe148Val
Coding: c.442T>G
MANE Select: NM_002633
dbSNP: rs755467080
Type: single nucleotide variant
Location: chr1:63629974 (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 148: 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-phe148val (accessed [today's date]).

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