Is MAGI2 p.Pro1240= (c.3720C>T) pathogenic?

MAGI2 p.Pro1240= (c.3720C>T) is classified Likely benign in MAGI2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-08-07). Very rare (popmax 0.00365%, nfe).

How common is MAGI2 p.Pro1240= (c.3720C>T) in the general population?

MAGI2 p.Pro1240= (c.3720C>T) is very rare (popmax 0.00365%, nfe) (gnomAD).

MAGI2 p.Pro1240=

c.3720C>T · rs760834788 · VCV3030925

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00365%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.119	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.2	GERP 0.77, phastCons 1
Overall
CADD	15.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00365% European (non-Finnish) · 43/1,177,440 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.00286% 46/1,606,520 alleles · very rare exomes 44/1,454,380 · genomes 2/152,140 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00365%	27,382
Admixed American	0.00169%	59,088
Remaining individualsnot grpmax-eligible	0.00161%	62,190
African / African-American	0.00134%	74,682

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: MAGI2
Protein: p.Pro1240=
Coding: c.3720C>T
MANE Select: NM_012301
dbSNP: rs760834788
Type: single nucleotide variant
Location: chr7:78019963 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 5 PDB
Residue 1240: the 'disordered' region

Full MAGI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAGI2 p.Pro1240His Uncertain significance ★ ⚠ same residue
MAGI2 p.Pro1240Ser Uncertain significance ★ ⚠ same residue
MAGI2 p.Ala1028Val Uncertain significance ★★ ⚠ same type
MAGI2 p.Ala1247Thr Uncertain significance ★★ ⚠ same type
MAGI2 p.Ala1271Thr Uncertain significance ★★ ⚠ same type
MAGI2 p.Ala1453Thr Uncertain significance ★★ ⚠ same type
MAGI2 p.Ala274Thr Uncertain significance ★★ ⚠ same type
MAGI2 p.Ala620Gly Uncertain significance ★★ ⚠ 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/magi2-p-pro1240 (accessed [today's date]).

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