Is MAG p.Arg508fs (c.1523_1530del) pathogenic?

MAG p.Arg508fs (c.15231530del) is classified Uncertain significance in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Absent from gnomAD; Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Arg508fs (c.1523_1530del)?

MAG p.Arg508fs (c.1523_1530del) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Arg508fs (c.1523_1530del) in the general population?

MAG p.Arg508fs (c.1523_1530del) is absent from gnomAD (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.Arg508fs

c.1523_1530del · rs2513601134 · VCV2857246

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary spastic paraplegia 75

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 0.37, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAG
Protein: p.Arg508fs
Coding: c.1523_1530del
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs2513601134
Type: Deletion
Location: chr19:35310550 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 508: a turn; 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

MAG p.Arg508Ter Pathogenic/Likely pathogenic ★★ same residue
MAG c.1232-3_1240del Likely pathogenic ★ same condition
MAG c.1520-3_1520-2del Likely pathogenic ★ same condition
MAG p.Val157fs Likely pathogenic ★ same condition
ERCC2 p.Phe508Leu Uncertain significance ★ ⚠ same residue
MAG p.Ala307Val Uncertain significance ★★ ⚠ same condition
MAG p.Ala490Thr Uncertain significance ★★ ⚠ same condition
MAG p.Arg316Leu 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-arg508fs (accessed [today's date]).

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