Is AMZ2 p.Gly153= (c.459G>A) pathogenic?

AMZ2 p.Gly153= (c.459G>A) is classified Likely benign in AMZ2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-19). Ultra-rare (popmax 0.0832%, afr); Associated with AMZ2-related disorder.

What condition is associated with AMZ2 p.Gly153= (c.459G>A)?

AMZ2 p.Gly153= (c.459G>A) is associated with AMZ2-related disorder (ClinVar).

How common is AMZ2 p.Gly153= (c.459G>A) in the general population?

AMZ2 p.Gly153= (c.459G>A) is ultra-rare (popmax 0.0832%, afr) (gnomAD).

AMZ2 p.Gly153=

c.459G>A · rs61739674 · VCV3046922

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0832%, afr)

Conditions

AMZ2-related disorder

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 0.74	GERP -0.22, phastCons 0.89
Overall
CADD	8.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0832% African / African-American · 62/74,494 alleles

Filtering AF 0.0665% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0606%

Overall 0.00522% 84/1,608,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0832%	1,202
Middle Eastern	0.0165%	6,052
Remaining individualsnot grpmax-eligible	0.0161%	6,230
Admixed American	0.0103%	9,735
South Asian	0.00223%	44,747
European (non-Finnish)	0.000254%	392,950

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: AMZ2
Protein: p.Gly153=
Coding: c.459G>A
MANE Select: NM_016627
dbSNP: rs61739674
Type: single nucleotide variant
Location: chr17:68251051 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.55

Full AMZ2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AMZ2-related disorder

Similar variants

AMZ2 c.586+8G>A Likely benign same condition
AMZ2 p.Ala356= Benign same condition
AMZ2 p.Asn30Asp Benign same condition
AMZ2 p.Gly198= Benign same condition
AMZ2 p.His331Arg Benign same condition
AMZ2 p.Ile256= Likely benign same condition
AMZ2 p.Ala117Thr Uncertain significance ★ ⚠ same type
AMZ2 p.Ala269Val 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/amz2-p-gly153 (accessed [today's date]).

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