Is PGM3 p.Phe542Val (c.1624T>G) pathogenic?

PGM3 p.Phe542Val (c.1624T>G) is classified Uncertain significance in PGM3 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.0828); Absent from gnomAD v4.1; Associated with immunodeficiency 23.

What condition is associated with PGM3 p.Phe542Val (c.1624T>G)?

PGM3 p.Phe542Val (c.1624T>G) is associated with immunodeficiency 23 (ClinVar).

How common is PGM3 p.Phe542Val (c.1624T>G) in the general population?

PGM3 p.Phe542Val (c.1624T>G) is absent from gnomAD v4.1 (gnomAD).

How is PGM3-CDG inherited?

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

What do computational predictors say about PGM3 p.Phe542Val (c.1624T>G)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

PGM3 p.Phe542Val

c.1624T>G · VCV3382982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 23

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.8	GERP 0.071, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	21.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PGM3
Protein: p.Phe542Val
Coding: c.1624T>G
MANE Select: NM_015599
Type: single nucleotide variant
Location: chr6:83169239 (GRCh38)

Full PGM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 23 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PGM3-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

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/pgm3-p-phe542val (accessed [today's date]).

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