Is MAG p.Val72= (c.216G>C) pathogenic?

MAG p.Val72= (c.216G>C) is classified Likely benign in MAG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-23). Ultra-rare (popmax 0.0657%, mid); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Val72= (c.216G>C)?

MAG p.Val72= (c.216G>C) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Val72= (c.216G>C) in the general population?

MAG p.Val72= (c.216G>C) is ultra-rare (popmax 0.0657%, mid) (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.Val72=

c.216G>C · rs200631477 · VCV706192

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

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 5.1	GERP 1.4, phastCons 1
Overall
CADD	8.671	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.0167% 270/1,613,896 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.22%	455
Middle Easterngrpmax	0.0657%	1,521
Remaining individualsnot grpmax-eligible	0.0464%	2,155
South Asian	0.0198%	5,060
Admixed American	0.0167%	6,000
European (non-Finnish)	0.0122%	8,195

Ashkenazi Jewish 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.Val72=
Coding: c.216G>C
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs200631477
Type: single nucleotide variant
Location: chr19:35295782 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 72: the helicase atp-binding domain; a β-strand

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.Tyr72= 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
MAG p.Arg465His Uncertain significance ★★ ⚠ same condition
MAG p.Arg563Cys 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-val72 (accessed [today's date]).

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