Is MAGED2 p.Lys397= (c.1191G>A) pathogenic?

MAGED2 p.Lys397= (c.1191G>A) is classified Benign in MAGED2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). Very rare (popmax 0.00983%, nfe).

How common is MAGED2 p.Lys397= (c.1191G>A) in the general population?

MAGED2 p.Lys397= (c.1191G>A) is very rare (popmax 0.00983%, nfe) (gnomAD).

MAGED2 p.Lys397=

c.1191G>A · rs138363965 · VCV2893515

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00983%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7	GERP 0.96, phastCons 1
Overall
CADD	10.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00983% European (non-Finnish) · 88/895,403 alleles

Filtering AF 0.00813% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00755%

Overall 0.00793% 96/1,209,952 alleles · very rare exomes 87/1,097,409 · genomes 9/112,543 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0126%	7,927
European (non-Finnish)grpmax	0.00983%	10,175
African / African-American	0.00349%	28,685

Remaining individuals 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: MAGED2
Protein: p.Lys397=
Coding: c.1191G>A
MANE Select: NM_177433
dbSNP: rs138363965
Type: single nucleotide variant
Location: chrX:54813143 (GRCh38)
Structure: AlphaFold pLDDT 59.89
Residue 397: the mage domain

Full MAGED2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAGED2 p.Ala389Gly Uncertain significance ★★ ⚠ same type
MAGED2 p.Ala97Gly Uncertain significance ★★ ⚠ same type
MAGED2 p.Arg257His Uncertain significance ★★ ⚠ same type
MAGED2 p.Pro153Ser Uncertain significance ★★ ⚠ same type
MAGED2 p.Pro436Ser Uncertain significance ★★ ⚠ same type
MAGED2 c.1085+101A>G Benign ★★ same type
MAGED2 c.1166-46C>A Benign ★★ same type
MAGED2 c.1208+122G>C Benign ★★ same type

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/maged2-p-lys397 (accessed [today's date]).

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