Is AMZ1 p.Pro169= (c.507A>G) pathogenic?

AMZ1 p.Pro169= (c.507A>G) is classified Likely benign in AMZ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-29). Very rare (popmax 0.00133%, afr).

How common is AMZ1 p.Pro169= (c.507A>G) in the general population?

AMZ1 p.Pro169= (c.507A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

AMZ1 p.Pro169=

c.507A>G · rs1583172032 · VCV755779

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 -9.4	GERP -4.2
Overall
CADD	0.029	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,018 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,460,780 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,018
European (non-Finnish)	0.000254%	393,320

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: AMZ1
Protein: p.Pro169=
Coding: c.507A>G
MANE Select: NM_001384743
dbSNP: rs1583172032
Type: single nucleotide variant
Location: chr7:2708622 (GRCh38)
Gene constraint: LOEUF 1.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.62

Full AMZ1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMZ1 p.Arg481Ter Likely benign ★★ same type
AMZ1 p.Pro394Leu Likely benign ★★ same type
AMZ1 p.Ala122Pro Uncertain significance ★ ⚠ same type
AMZ1 p.Ala172Val Uncertain significance ★ ⚠ same type
AMZ1 p.Ala188Asp Uncertain significance ★ ⚠ same type
AMZ1 p.Ala208Ser Uncertain significance ★ ⚠ same type
AMZ1 p.Ala208Thr Uncertain significance ★ ⚠ same type
AMZ1 p.Ala230Val 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/amz1-p-pro169 (accessed [today's date]).

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