Is AMZ2 p.Arg284Pro (c.851G>C) pathogenic?

AMZ2 p.Arg284Pro (c.851G>C) is classified Uncertain significance in AMZ2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.9507); Absent from gnomAD v4.1.

How common is AMZ2 p.Arg284Pro (c.851G>C) in the general population?

AMZ2 p.Arg284Pro (c.851G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMZ2 p.Arg284Pro (c.851G>C)?

AlphaMissense predicts likely pathogenic (score 0.9507) — an in-silico prediction, not a clinical call.

AMZ2 p.Arg284Pro

c.851G>C · VCV4835272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9507 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9507	likely pathogenic · top 8% in AMZ2
REVEL	0.505	indeterminate
SaProt	LLR -10.96	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,778 bp · p 0.078 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AMZ2
Protein: p.Arg284Pro
Coding: c.851G>C
MANE Select: NM_016627
Type: single nucleotide variant
Location: chr17:68255800 (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

Similar variants

AMZ2 p.Ala117Thr Uncertain significance ★ ⚠ same type
AMZ2 p.Ala269Val Uncertain significance ★ ⚠ same type
AMZ2 p.Arg101Lys Uncertain significance ★ ⚠ same type
AMZ2 p.Arg247Gln Uncertain significance ★ ⚠ same type
AMZ2 p.Arg263Gln Uncertain significance ★ ⚠ same type
AMZ2 p.Arg283Trp Uncertain significance ★ ⚠ same type
AMZ2 p.Arg35Cys Uncertain significance ★ ⚠ same type
AMZ2 p.Arg35His 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-arg284pro (accessed [today's date]).

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