Is MAG p.Pro147Ala (c.439C>G) pathogenic?

MAG p.Pro147Ala (c.439C>G) is classified Uncertain significance in MAG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-01). AlphaMissense: likely benign (0.0658); Ultra-rare (popmax 0.0553%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAG p.Pro147Ala (c.439C>G)?

MAG p.Pro147Ala (c.439C>G) is associated with Inborn genetic diseases, hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Pro147Ala (c.439C>G) in the general population?

MAG p.Pro147Ala (c.439C>G) is ultra-rare (popmax 0.0553%, nfe) (gnomAD).

What do computational predictors say about MAG p.Pro147Ala (c.439C>G)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

MAG p.Pro147Ala

c.439C>G · rs202205105 · VCV969102

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0553%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -6.42	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 1.8	GERP -0.88, phastCons 0.85
Overall
CADD	15.02	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0553% European (non-Finnish) · 648/1,171,310 alleles

Filtering AF 0.0517% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0504%

Overall 0.0486% 779/1,601,352 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.167%	599
Finnishnot grpmax-eligible	0.0831%	1,204
European (non-Finnish)grpmax	0.0553%	1,808
Remaining individualsnot grpmax-eligible	0.0259%	3,863
African / African-American	0.0134%	7,450
Admixed American	0.00337%	29,709
South Asian	0.00111%	89,940

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro147Ala
Coding: c.439C>G
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs202205105
Type: single nucleotide variant
Location: chr19:35299577 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 147: 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.Gln147Lys Uncertain significance ★ ⚠ same residue
ERCC2 p.Gln147= Likely benign ★ same residue
ERCC2 p.Gln147Ter Pathogenic 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-pro147ala (accessed [today's date]).

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