Is MAGI2 p.Phe911= (c.2733C>T) pathogenic?

MAGI2 p.Phe911= (c.2733C>T) is classified Likely benign in MAGI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-13). Very rare (popmax 0.00704%, nfe).

How common is MAGI2 p.Phe911= (c.2733C>T) in the general population?

MAGI2 p.Phe911= (c.2733C>T) is very rare (popmax 0.00704%, nfe) (gnomAD).

MAGI2 p.Phe911=

c.2733C>T · VCV4896380

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00704%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.1	GERP -4.9
Overall
CADD	11.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00704% European (non-Finnish) · 83/1,179,110 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00533%

Overall 0.0414% 667/1,612,162 alleles · very rare exomes 527/1,459,836 · genomes 140/152,326 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.87%	115
Amishnot grpmax-eligible	0.11%	912
Remaining individualsnot grpmax-eligible	0.0384%	2,603
European (non-Finnish)grpmax	0.00704%	14,206
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
Admixed American	0.00167%	59,778

Finnish 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: MAGI2
Protein: p.Phe911=
Coding: c.2733C>T
MANE Select: NM_012301
Type: single nucleotide variant
Location: chr7:78160137 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 5 PDB
Residue 911: the 'disordered' region

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

Similar variants

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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
MAGI2 p.Ala809Ser Uncertain significance ★★ ⚠ same type
MAGI2 p.Ala899Pro 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-phe911 (accessed [today's date]).

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