Is MAG p.His599Pro (c.1796A>C) pathogenic?

MAG p.His599Pro (c.1796A>C) is classified Uncertain significance in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-11). AlphaMissense: likely benign (0.0976); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MAG p.His599Pro (c.1796A>C)?

MAG p.His599Pro (c.1796A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MAG p.His599Pro (c.1796A>C) in the general population?

MAG p.His599Pro (c.1796A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAG p.His599Pro (c.1796A>C)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

MAG p.His599Pro

c.1796A>C · rs370759759 · VCV2228739

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.38	indeterminate
SaProt	LLR -6.21	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 9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 18 kb · p 0.052 · regional, not allelic
Overall
CADD	23.9	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

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.His599Pro
Coding: c.1796A>C
MANE Select: NM_002361
dbSNP: rs370759759
Type: single nucleotide variant
Location: chr19:35313369 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.53
Residue 599: the 'required for normal axon myelination in the central nervous system' region; the 'disordered' region

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

MAG p.Ala490Thr Uncertain significance ★★ ⚠ same condition
MAG p.Arg316Leu Uncertain significance ★★ ⚠ same condition
MAG p.Arg465His Uncertain significance ★★ ⚠ same condition
MAG p.Arg563Cys Uncertain significance ★★ ⚠ same condition
MAG p.Arg576His Uncertain significance ★★ ⚠ same condition
MAG p.Arg587Gln Uncertain significance ★★ ⚠ same condition
MAG p.Asn106Lys Uncertain significance ★★ ⚠ same condition
MAG p.Asn62Ser 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-his599pro (accessed [today's date]).

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