Is MAG p.Ala151Val (c.452C>T) pathogenic?

MAG p.Ala151Val (c.452C>T) is classified Conflicting classifications of pathogenicity in MAG (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.179); Rare (popmax 0.637%, nfe); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Ala151Val (c.452C>T)?

MAG p.Ala151Val (c.452C>T) is associated with hereditary spastic paraplegia 75, hereditary spastic paraplegia (ClinVar).

How common is MAG p.Ala151Val (c.452C>T) in the general population?

MAG p.Ala151Val (c.452C>T) is rare (popmax 0.637%, 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.Ala151Val (c.452C>T)?

AlphaMissense predicts likely benign (score 0.179) — an in-silico prediction, not a clinical call.

MAG p.Ala151Val

c.452C>T · rs144553163 · VCV424686

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.179 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.637%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary spastic paraplegia 75

Computational evidence

Protein change
AlphaMissense	0.179	likely benign
REVEL	0.37	indeterminate
SaProt	LLR -8.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.6, phastCons 0.98
Overall
CADD	22.9	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 0.637% European (non-Finnish) · 7,470/1,172,284 alleles

Filtering AF 0.625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.62%

Overall 0.53% 8,495/1,602,818 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.637%	157
South Asian	0.511%	196
Middle Eastern	0.482%	207
Remaining individualsnot grpmax-eligible	0.412%	243
Admixed American	0.193%	517
African / African-American	0.126%	795
Finnishnot grpmax-eligible	0.0972%	1,029
Ashkenazi Jewishnot grpmax-eligible	0.034%	2,937

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.Ala151Val
Coding: c.452C>T
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs144553163
Type: single nucleotide variant
Location: chr19:35299590 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 151: 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

Also linked: hereditary spastic paraplegia

For Autosomal recessive spastic paraplegia type 75 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

ERCC2 p.Ser151= 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-ala151val (accessed [today's date]).

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