Is MAG p.Pro590= (c.1770C>T) pathogenic?

MAG p.Pro590= (c.1770C>T) is classified Likely benign in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-10). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Pro590= (c.1770C>T)?

MAG p.Pro590= (c.1770C>T) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Pro590= (c.1770C>T) in the general population?

MAG p.Pro590= (c.1770C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Autosomal recessive spastic paraplegia type 75 inherited?

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

MAG p.Pro590=

c.1770C>T · rs201562930 · VCV1950732

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

hereditary spastic paraplegia 75

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 2.3, phastCons 1
Overall
CADD	9.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 0.000124% 2/1,614,150 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,036
European (non-Finnish)grpmax	8.47e-05%	1,180,016

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MAG
Protein: p.Pro590=
Coding: c.1770C>T
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs201562930
Type: single nucleotide variant
Location: chr19:35313343 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 590: a β-strand; the 'mediates interaction with mms19' region

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

Disease context

hereditary spastic paraplegia 75 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 75 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

ERCC2 p.Asn590Lys Uncertain significance ★ ⚠ same residue
MAG p.Pro590Thr Uncertain significance ★ ⚠ same residue
ERCC2 p.Asn590= Likely benign ★ same residue
MAG p.Arg508Ter Pathogenic/Likely pathogenic ★★ same condition
MAG p.Ala307Val Uncertain significance ★★ ⚠ same condition
MAG p.Ala490Thr Uncertain significance ★★ ⚠ same condition
MAG p.Arg316Leu Uncertain significance ★★ ⚠ same condition
MAG p.Arg425Gln Uncertain significance ★★ ⚠ 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/mag-p-pro590 (accessed [today's date]).

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