Is AMZ2 p.Ile256= (c.768C>T) pathogenic?

AMZ2 p.Ile256= (c.768C>T) is classified Likely benign in AMZ2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-18). Ultra-rare (popmax 0.0311%, nfe); Associated with AMZ2-related disorder.

What condition is associated with AMZ2 p.Ile256= (c.768C>T)?

AMZ2 p.Ile256= (c.768C>T) is associated with AMZ2-related disorder (ClinVar).

How common is AMZ2 p.Ile256= (c.768C>T) in the general population?

AMZ2 p.Ile256= (c.768C>T) is ultra-rare (popmax 0.0311%, nfe) (gnomAD).

AMZ2 p.Ile256=

c.768C>T · rs138911562 · VCV3041066

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0311%, nfe)

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 -16	GERP -3.7
Overall
CADD	0.494	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0311% European (non-Finnish) · 367/1,179,948 alleles

Filtering AF 0.0285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0274%

Overall 0.0239% 386/1,613,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0311%	3,215
Middle Eastern	0.0164%	6,084
East Asian	0.00668%	14,964
Admixed American	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0048%	20,827
South Asian	0.00439%	22,768
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
Finnishnot grpmax-eligible	0.00312%	32,018
African / African-American	0.00267%	37,454

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.Ile256=
Coding: c.768C>T
MANE Select: NM_016627
dbSNP: rs138911562
Type: single nucleotide variant
Location: chr17:68255717 (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 p.Ile256Met Uncertain significance ★ ⚠ same residue
AMZ2 c.586+8G>A Likely benign same condition
AMZ2 p.Ala356= Benign same condition
AMZ2 p.Asn30Asp Benign same condition
AMZ2 p.Gly153= Likely benign same condition
AMZ2 p.Gly198= Benign same condition
AMZ2 p.His331Arg Benign same condition
AMZ2 p.Ala117Thr 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-ile256 (accessed [today's date]).

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