Is MAG p.Ser84Arg (c.252C>A) pathogenic?

MAG p.Ser84Arg (c.252C>A) is classified Uncertain significance in MAG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.926); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAG p.Ser84Arg (c.252C>A)?

MAG p.Ser84Arg (c.252C>A) is associated with Inborn genetic diseases, hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Ser84Arg (c.252C>A) in the general population?

MAG p.Ser84Arg (c.252C>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about MAG p.Ser84Arg (c.252C>A)?

AlphaMissense predicts likely pathogenic (score 0.926) — an in-silico prediction, not a clinical call.

MAG p.Ser84Arg

c.252C>A · rs763042714 · VCV1432660

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.926	likely pathogenic
REVEL	0.3	indeterminate
SaProt	LLR -6.07	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -2.2, phastCons 1
Overall
CADD	21.8	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 0.000424% European (non-Finnish) · 5/1,180,022 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,844 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.Ser84Arg
Coding: c.252C>A
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs763042714
Type: single nucleotide variant
Location: chr19:35295818 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 84: the helicase atp-binding domain; an α-helix

Full MAG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 75

Similar variants

ERCC2 p.Ile84Thr Uncertain significance ★ ⚠ same residue
ERCC2 p.Ile84= Likely benign ★ same residue
ERCC2 p.Ile84Val Uncertain significance ★ ⚠ same residue
ERCC2 p.Ala725Pro Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Arg616Pro Pathogenic ★★ same condition
MAG p.Arg508Ter Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Ala108Thr Uncertain significance ★★ ⚠ same condition
ERCC2 p.Ala144Val 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-ser84arg (accessed [today's date]).

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