Is MAG p.Val241fs (c.719dup) pathogenic?

MAG p.Val241fs (c.719dup) is classified Pathogenic in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). Very rare (popmax 0.000617%, nfe); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Val241fs (c.719dup)?

MAG p.Val241fs (c.719dup) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Val241fs (c.719dup) in the general population?

MAG p.Val241fs (c.719dup) is very rare (popmax 0.000617%, 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.Val241fs

c.719dup · rs770601245 · VCV1478560

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000617%, nfe)

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 11	GERP 1.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000617% European (non-Finnish) · 7/1,133,942 alleles

Filtering AF 0.000257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000165%

Overall 0.000509% 7/1,375,502 alleles · very rare

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.Val241fs
Coding: c.719dup
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs770601245
Type: Duplication
Location: chr19:35300147 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 241: the helicase atp-binding domain; an α-helix

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.Val241= Likely benign ★ same residue
ERCC2 p.Asn241= Likely benign ★★ same residue
ERCC2 p.Asn241Ser Uncertain significance ★ ⚠ same residue
ERCC2 p.Asn241Thr Uncertain significance ★ ⚠ same residue
MAG p.Ile529_Val530insLeuIleAlaIle Uncertain significance ★ same condition
MAG p.Val241Glu Uncertain significance ★ ⚠ same residue
MAG p.Val241Met Uncertain significance ★ ⚠ same residue
MAG p.Arg508Ter 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/mag-p-val241fs (accessed [today's date]).

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