Is MAG p.Val302Asp (c.905T>A) pathogenic?

MAG p.Val302Asp (c.905T>A) is classified Likely benign in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.2374); Rare (popmax 0.941%, eas); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Val302Asp (c.905T>A)?

MAG p.Val302Asp (c.905T>A) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Val302Asp (c.905T>A) in the general population?

MAG p.Val302Asp (c.905T>A) is rare (popmax 0.941%, eas) (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.Val302Asp (c.905T>A)?

AlphaMissense predicts likely benign (score 0.2374) — an in-silico prediction, not a clinical call.

MAG p.Val302Asp

c.905T>A · rs76943436 · VCV711281

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2374 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.941%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary spastic paraplegia 75

Computational evidence

Protein change
AlphaMissense	0.2374	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.1, phastCons 1
Overall
CADD	24.6	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 0.941% East Asian · 422/44,834 alleles

Filtering AF 0.867% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.838%

Overall 0.0265% 423/1,598,580 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.941%	106
Remaining individualsnot grpmax-eligible	0.0016%	62,356

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.Val302Asp
Coding: c.905T>A
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs76943436
Type: single nucleotide variant
Location: chr19:35300339 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB

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.Asp302Asn Uncertain significance ★★ ⚠ same residue
ERCC2 p.Asp302= 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

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-val302asp (accessed [today's date]).

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