Is AMZ1 p.Ser69Arg (c.207C>G) pathogenic?

AMZ1 p.Ser69Arg (c.207C>G) is classified Uncertain significance in AMZ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-25). AlphaMissense: likely pathogenic (0.788); Very rare (popmax 0.00445%, eas).

How common is AMZ1 p.Ser69Arg (c.207C>G) in the general population?

AMZ1 p.Ser69Arg (c.207C>G) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about AMZ1 p.Ser69Arg (c.207C>G)?

AlphaMissense predicts likely pathogenic (score 0.788) — an in-silico prediction, not a clinical call.

AMZ1 p.Ser69Arg

c.207C>G · VCV4048406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.788 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.788	likely pathogenic
REVEL	0.264	benign-leaning
SaProt	LLR -3.87	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP 0.18, phastCons 1
Regional constraint	o/e 1.53	unconstrained · MANE · 12 kb · p 2.2e-43 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,902 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,612,098 alleles · very rare

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.Ser69Arg
Coding: c.207C>G
MANE Select: NM_001384743
Type: single nucleotide variant
Location: chr7:2700658 (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-ser69arg (accessed [today's date]).

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