Is MAG p.Pro380= (c.1140G>A) pathogenic?

MAG p.Pro380= (c.1140G>A) is classified Benign in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-11). Rare (popmax 0.591%, eas); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Pro380= (c.1140G>A)?

MAG p.Pro380= (c.1140G>A) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Pro380= (c.1140G>A) in the general population?

MAG p.Pro380= (c.1140G>A) is rare (popmax 0.591%, eas) (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.Pro380=

c.1140G>A · rs200135379 · VCV772706

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.591%, eas)

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 -12	GERP -4.4
Overall
CADD	0.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.591% East Asian · 265/44,872 alleles

Filtering AF 0.532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.509%

Overall 0.0176% 284/1,614,168 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.591%	169
Remaining individualsnot grpmax-eligible	0.0128%	7,814
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	30,014
South Asian	0.0011%	91,080
European (non-Finnish)	0.000593%	168,577

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.Pro380=
Coding: c.1140G>A
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs200135379
Type: single nucleotide variant
Location: chr19:35302617 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 380: 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.Pro380Ser Uncertain significance ★★ ⚠ same residue
MAG p.Pro380Arg Uncertain significance ★ ⚠ same residue
ERCC2 p.Arg380Gln Uncertain significance ★★ ⚠ same residue
ERCC2 p.Arg380Gly Uncertain significance ★ ⚠ same residue
ERCC2 p.Arg380Pro Uncertain significance ★ ⚠ same residue
MAG p.Pro380Leu Uncertain significance ★ ⚠ same residue
ERCC2 p.Arg380= Likely benign ★ 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-pro380 (accessed [today's date]).

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