Is MAG p.His82= (c.246C>T) pathogenic?

MAG p.His82= (c.246C>T) is classified Benign/Likely benign in MAG (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-01). Low-frequency (popmax 1.11%, afr); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.His82= (c.246C>T)?

MAG p.His82= (c.246C>T) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.His82= (c.246C>T) in the general population?

MAG p.His82= (c.246C>T) is low-frequency (popmax 1.11%, afr) (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.His82=

c.246C>T · rs142156011 · VCV976540

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.11%, afr)

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 -8.7	GERP -3.5
Overall
CADD	4.651	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.11% African / African-American · 836/75,026 alleles

Filtering AF 1.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.0577% 932/1,613,932 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.11%	90
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Admixed American	0.0567%	1,765
Middle Eastern	0.033%	3,029
European (non-Finnish)	0.00186%	53,637
South Asian	0.0011%	91,074

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.His82=
Coding: c.246C>T
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs142156011
Type: single nucleotide variant
Location: chr19:35295812 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 82: 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.Lys82Ter Pathogenic ★ 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-his82 (accessed [today's date]).

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