Is MAG p.Ala307Val (c.920C>T) pathogenic?

MAG p.Ala307Val (c.920C>T) is classified Uncertain significance in MAG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-19). AlphaMissense: likely pathogenic (0.6402); Very rare (popmax 0.00017%, nfe); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Ala307Val (c.920C>T)?

MAG p.Ala307Val (c.920C>T) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Ala307Val (c.920C>T) in the general population?

MAG p.Ala307Val (c.920C>T) is very rare (popmax 0.00017%, 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.Ala307Val (c.920C>T)?

AlphaMissense predicts likely pathogenic (score 0.6402) — an in-silico prediction, not a clinical call.

MAG p.Ala307Val

c.920C>T · rs766654454 · VCV2051813

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6402 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary spastic paraplegia 75

Computational evidence

Protein change
AlphaMissense	0.6402	likely pathogenic
REVEL	0.569	indeterminate
SaProt	LLR -10.23	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.1, phastCons 1
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,034 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,596,742 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.Ala307Val
Coding: c.920C>T
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs766654454
Type: single nucleotide variant
Location: chr19:35300354 (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.Asn307His Uncertain significance ★ ⚠ same residue
ERCC2 p.Asn307Lys Uncertain significance ★ ⚠ same residue
ERCC2 p.Asn307Ser Uncertain significance ★ ⚠ same residue
ERCC2 p.Asn307= Likely benign ★ same residue
MAG p.Arg508Ter Pathogenic/Likely pathogenic ★★ same condition
MAG p.Ala490Thr Uncertain significance ★★ ⚠ same condition
MAG p.Arg316Leu Uncertain significance ★★ ⚠ same condition
MAG p.Arg425Gln 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-ala307val (accessed [today's date]).

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