Is MAG p.Ser76= (c.228G>T) pathogenic?

MAG p.Ser76= (c.228G>T) is classified Likely benign in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-20). Ultra-rare (popmax 0.01%, amr); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Ser76= (c.228G>T)?

MAG p.Ser76= (c.228G>T) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Ser76= (c.228G>T) in the general population?

MAG p.Ser76= (c.228G>T) is ultra-rare (popmax 0.01%, amr) (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.Ser76=

c.228G>T · rs142334011 · VCV1921307

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

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 -3.6	GERP -5
Overall
CADD	1.278	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,960 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000992% 16/1,613,564 alleles · ultra-rare exomes 5/1,461,598 · genomes 11/151,966 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,993
African / African-American	0.00802%	12,467
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000254%	393,331

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.Ser76=
Coding: c.228G>T
MANE Select: NM_002361
dbSNP: rs142334011
Type: single nucleotide variant
Location: chr19:35295794 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 76: the helicase atp-binding domain; a UniProt-annotated variant site (in xp-d)

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.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
MAG p.Arg563His 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-ser76 (accessed [today's date]).

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