Is MAG p.Ala283= (c.849G>A) pathogenic?

MAG p.Ala283= (c.849G>A) is classified Likely benign in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Ultra-rare (popmax 0.0171%, nfe); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Ala283= (c.849G>A)?

MAG p.Ala283= (c.849G>A) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Ala283= (c.849G>A) in the general population?

MAG p.Ala283= (c.849G>A) is ultra-rare (popmax 0.0171%, 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.Ala283=

c.849G>A · rs140197131 · VCV706853

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, 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 -14	GERP -4
Overall
CADD	0.577	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0171% European (non-Finnish) · 201/1,178,760 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0143%

Overall 0.0133% 213/1,599,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0171%	5,864
Remaining individualsnot grpmax-eligible	0.0129%	7,779
Admixed American	0.00502%	19,923
African / African-American	0.00134%	74,892

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.Ala283=
Coding: c.849G>A
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs140197131
Type: single nucleotide variant
Location: chr19:35300283 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 283: 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

ERCC2 p.Asp283= Likely benign ★★ same residue
ERCC2 p.Asp283Ala Uncertain significance ★ ⚠ same residue
ERCC2 p.Asp283Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
ERCC2 p.Asp283Tyr Uncertain significance ★ ⚠ same residue
ERCC2 p.Asp283Val Uncertain significance ★ ⚠ same residue
MAG p.Arg508Ter Pathogenic/Likely pathogenic ★★ same condition
MAG p.Ala307Val Uncertain significance ★★ ⚠ same condition
MAG p.Ala490Thr 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-ala283 (accessed [today's date]).

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