Is MAG p.Ser233Arg (c.699C>G) pathogenic?

MAG p.Ser233Arg (c.699C>G) is classified Uncertain significance in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: ambiguous (0.3788); Very rare (popmax 0.000458%, nfe); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Ser233Arg (c.699C>G)?

MAG p.Ser233Arg (c.699C>G) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Ser233Arg (c.699C>G) in the general population?

MAG p.Ser233Arg (c.699C>G) is very rare (popmax 0.000458%, 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.

What do computational predictors say about MAG p.Ser233Arg (c.699C>G)?

AlphaMissense predicts ambiguous (score 0.3788) — an in-silico prediction, not a clinical call.

MAG p.Ser233Arg

c.699C>G · rs1348797051 · VCV1421065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3788 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000458%, nfe)

Conditions

hereditary spastic paraplegia 75

Computational evidence

Protein change
AlphaMissense	0.3788	ambiguous
REVEL	0.525	indeterminate
SaProt	LLR -5.89	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -1.4, phastCons 1
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000458% European (non-Finnish) · 5/1,090,798 alleles

Filtering AF 0.000134% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.8e-05%

Overall 0.000346% 5/1,444,136 alleles · very rare

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.Ser233Arg
Coding: c.699C>G
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs1348797051
Type: single nucleotide variant
Location: chr19:35299837 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 233: the helicase atp-binding domain; a β-strand

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.Phe233= Benign/Likely benign ★★ 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-ser233arg (accessed [today's date]).

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