Is MAG p.Ser351= (c.1053C>T) pathogenic?

MAG p.Ser351= (c.1053C>T) is classified Likely benign in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Ser351= (c.1053C>T)?

MAG p.Ser351= (c.1053C>T) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Ser351= (c.1053C>T) in the general population?

MAG p.Ser351= (c.1053C>T) is very rare (popmax 8.47e-05%, 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.

MAG p.Ser351=

c.1053C>T · rs2066456035 · VCV1148577

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

hereditary spastic paraplegia 75

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.58	acceptor gain · deltas
Pangolin	Δ0.27	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 1.1, phastCons 1
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,050 alleles

Overall 6.84e-05% 1/1,461,892 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.Ser351=
Coding: c.1053C>T
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs2066456035
Type: single nucleotide variant
Location: chr19:35302530 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 351: 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.Gln351= Likely benign ★★ same residue
ERCC2 p.Gln351Ter Pathogenic ★ same residue
ERCC2 p.Gln351Arg Uncertain significance ★ ⚠ same residue
ERCC2 p.Gln351Pro 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

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-ser351 (accessed [today's date]).

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