Is AMIGO2 p.Glu494= (c.1482G>A) pathogenic?

AMIGO2 p.Glu494= (c.1482G>A) is classified Benign in AMIGO2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 5.9%, afr) — too common for a highly-penetrant pathogenic allele.

AMIGO2 p.Glu494=

Q: How common is AMIGO2 p.Glu494= (c.1482G>A) in the general population?

AMIGO2 p.Glu494= (c.1482G>A) is common (popmax 5.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1482G>A · rs11836128 · VCV779523

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.9%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.3, phastCons 1
Overall
CADD	10.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.9% African / African-American · 4,425/75,032 alleles

Filtering AF 5.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.69%

Overall 0.371% 5,994/1,614,150 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.9%	17
Middle Eastern	0.907%	110
Remaining individualsnot grpmax-eligible	0.658%	152
Admixed American	0.573%	174
European (non-Finnish)	0.0622%	1,608
South Asian	0.0274%	3,643

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: AMIGO2
Protein: p.Glu494=
Coding: c.1482G>A
MANE Select: NM_001370299
dbSNP: rs11836128
Type: single nucleotide variant
Location: chr12:47077521 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.93

Full AMIGO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMIGO2 p.Ala300Thr Uncertain significance ★ ⚠ same type
AMIGO2 p.Ala520Val Uncertain significance ★ ⚠ same type
AMIGO2 p.Ala93Thr Uncertain significance ★ ⚠ same type
AMIGO2 p.Arg203Gly Uncertain significance ★ ⚠ same type
AMIGO2 p.Arg245Pro Uncertain significance ★ ⚠ same type
AMIGO2 p.Arg246Ser Uncertain significance ★ ⚠ same type
AMIGO2 p.Arg261Ser Uncertain significance ★ ⚠ same type
AMIGO2 p.Arg270Leu 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/amigo2-p-glu494 (accessed [today's date]).

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