Is MAG p.Arg77Ser (c.229C>A) pathogenic?

MAG p.Arg77Ser (c.229C>A) is classified Uncertain significance in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-23). AlphaMissense: likely pathogenic (0.9505); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MAG p.Arg77Ser (c.229C>A)?

MAG p.Arg77Ser (c.229C>A) is associated with Inborn genetic diseases (ClinVar).

How common is MAG p.Arg77Ser (c.229C>A) in the general population?

MAG p.Arg77Ser (c.229C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAG p.Arg77Ser (c.229C>A)?

AlphaMissense predicts likely pathogenic (score 0.9505) — an in-silico prediction, not a clinical call.

MAG p.Arg77Ser

c.229C>A · rs759019774 · VCV2528911

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9505 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9505	likely pathogenic
REVEL	0.213	benign-leaning
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Overall
CADD	27.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAG
Protein: p.Arg77Ser
Coding: c.229C>A
MANE Select: NM_000400 · reported on NM_002361
dbSNP: rs759019774
Type: single nucleotide variant
Location: chr19:35295795 (GRCh38)
Structure: AlphaFold pLDDT 87.74 · 55 PDB
Residue 77: 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.Val77Met Uncertain significance ★★ ⚠ same residue
ERCC2 p.Val77Leu Uncertain significance ★ ⚠ same residue
MAG p.Arg77Leu Uncertain significance ★★ ⚠ same residue
MAG p.Arg77His 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
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-arg77ser (accessed [today's date]).

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