Is MAG p.Val134Ala (c.401T>C) pathogenic?

MAG p.Val134Ala (c.401T>C) is classified Uncertain significance in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-27). AlphaMissense: likely benign (0.1452); Ultra-rare (popmax 0.0333%, sas); Associated with Inborn genetic diseases.

What condition is associated with MAG p.Val134Ala (c.401T>C)?

MAG p.Val134Ala (c.401T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MAG p.Val134Ala (c.401T>C) in the general population?

MAG p.Val134Ala (c.401T>C) is ultra-rare (popmax 0.0333%, sas) (gnomAD).

What do computational predictors say about MAG p.Val134Ala (c.401T>C)?

AlphaMissense predicts likely benign (score 0.1452) — an in-silico prediction, not a clinical call.

MAG p.Val134Ala

c.401T>C · VCV4624161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1452 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1452	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -6.86	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 6.1	GERP 2.4, phastCons 1
Overall
CADD	21.4	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 0.0333% South Asian · 29/87,042 alleles

Filtering AF 0.0238% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0206%

Overall 0.00183% 29/1,582,874 alleles · ultra-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.Val134Ala
Coding: c.401T>C
MANE Select: NM_000400 · reported on NM_002361
Type: single nucleotide variant
Location: chr19:35295967 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 134: the helicase atp-binding domain; a binding site; 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

Similar variants

ERCC2 p.Cys134Trp Uncertain significance ★★ ⚠ same residue
MAG p.Val134Ile Uncertain significance ★★ ⚠ same residue
ERCC2 p.Cys134Ter Likely pathogenic ★ same residue
ERCC2 p.Ala725Pro Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Arg616Pro Pathogenic ★★ same condition
ERCC2 p.Ala108Thr Uncertain significance ★★ ⚠ same condition
ERCC2 p.Ala144Val Uncertain significance ★★ ⚠ same condition
ERCC2 p.Ala226Thr 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-val134ala (accessed [today's date]).

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