Is MAG p.Ala394= (c.1182T>C) pathogenic?

MAG p.Ala394= (c.1182T>C) is classified Likely benign in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-14). Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Ala394= (c.1182T>C)?

MAG p.Ala394= (c.1182T>C) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Ala394= (c.1182T>C) in the general population?

MAG p.Ala394= (c.1182T>C) is absent from gnomAD v4.1 (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.Ala394=

c.1182T>C · rs2066457460 · VCV2124636

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -9.5	GERP -4.4
Overall
CADD	1.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAG
Protein: p.Ala394=
Coding: c.1182T>C
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs2066457460
Type: single nucleotide variant
Location: chr19:35302659 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 394: 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.Phe394Leu Uncertain significance ★★ ⚠ same residue
ERCC2 p.Phe394= Likely benign ★★ same residue
KLC3 p.Ala394Val 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
MAG p.Arg316Leu Uncertain significance ★★ ⚠ same condition
MAG p.Arg425Gln 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-ala394 (accessed [today's date]).

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