Is PGM3 p.Pro474Ser (c.1420C>T) pathogenic?

PGM3 p.Pro474Ser (c.1420C>T) is classified Uncertain significance in PGM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-27). AlphaMissense: likely pathogenic (0.778); Very rare (popmax 8.48e-05%, nfe).

How common is PGM3 p.Pro474Ser (c.1420C>T) in the general population?

PGM3 p.Pro474Ser (c.1420C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PGM3 p.Pro474Ser (c.1420C>T)?

AlphaMissense predicts likely pathogenic (score 0.778) — an in-silico prediction, not a clinical call.

PGM3 p.Pro474Ser

c.1420C>T · VCV4893295

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.778 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ 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	0.778	likely pathogenic
REVEL	0.423	indeterminate
SaProt	LLR -10.87	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.48e-05% European (non-Finnish) · 1/1,179,920 alleles

Overall 6.2e-05% 1/1,614,022 alleles · very rare exomes 1/1,461,750 · genomes 0/152,272 · joint denominator

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: PGM3
Protein: p.Pro474Ser
Coding: c.1420C>T
MANE Select: NM_015599
Type: single nucleotide variant
Location: chr6:83170424 (GRCh38)

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

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-pro474ser (accessed [today's date]).

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