Is MAG p.Arg214= (c.642G>A) pathogenic?

MAG p.Arg214= (c.642G>A) is classified Likely benign in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-19). Very rare (popmax 0.000956%, nfe); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Arg214= (c.642G>A)?

MAG p.Arg214= (c.642G>A) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Arg214= (c.642G>A) in the general population?

MAG p.Arg214= (c.642G>A) is very rare (popmax 0.000956%, 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.Arg214=

c.642G>A · rs1279257840 · VCV1531171

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000956%, 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 0.79	GERP -3.9, phastCons 1
Overall
CADD	8.151	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000956% European (non-Finnish) · 11/1,150,370 alleles

Filtering AF 0.000513% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000375%

Overall 0.000711% 11/1,546,814 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.Arg214=
Coding: c.642G>A
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs1279257840
Type: single nucleotide variant
Location: chr19:35299780 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 214: the helicase atp-binding domain

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.Asp214His Uncertain significance ★ ⚠ same residue
ERCC2 p.Asp214= 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

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-arg214 (accessed [today's date]).

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