Is MAG p.Val241Met (c.721G>A) pathogenic?

MAG p.Val241Met (c.721G>A) is classified Uncertain significance in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely benign (0.1003); Very rare (popmax 0.00137%, afr); Associated with Inborn genetic diseases.

What condition is associated with MAG p.Val241Met (c.721G>A)?

MAG p.Val241Met (c.721G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MAG p.Val241Met (c.721G>A) in the general population?

MAG p.Val241Met (c.721G>A) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about MAG p.Val241Met (c.721G>A)?

AlphaMissense predicts likely benign (score 0.1003) — an in-silico prediction, not a clinical call.

MAG p.Val241Met

c.721G>A · rs1343744680 · VCV3122048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1003 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1003	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -8.56	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 2.1	GERP -0.28, phastCons 0.99
Overall
CADD	19.02	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 0.00137% African / African-American · 1/73,098 alleles

Filtering AF 0.000638% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000491%

Overall 0.000912% 14/1,535,656 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	73,098
European (non-Finnish)	0.00114%	87,495

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.Val241Met
Coding: c.721G>A
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs1343744680
Type: single nucleotide variant
Location: chr19:35300155 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 241: 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

Similar variants

ERCC2 p.Asn241= Likely benign ★★ same residue
ERCC2 p.Asn241Thr Uncertain significance ★ ⚠ same residue
MAG p.Val241Glu Uncertain significance ★ ⚠ same residue
ERCC2 p.Asn241Ser Uncertain significance ★ ⚠ same residue
MAG p.Val241= Likely benign ★ same residue
ERCC2 p.Ala725Pro Pathogenic/Likely pathogenic ★★ same condition
ERCC2 p.Arg616Pro Pathogenic ★★ same condition
ERCC2 p.Ala108Thr 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-val241met (accessed [today's date]).

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