Is AMZ2 p.Ser55Pro (c.163T>C) pathogenic?

AMZ2 p.Ser55Pro (c.163T>C) is classified Uncertain significance in AMZ2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely pathogenic (0.792); Ultra-rare (popmax 0.0245%, eas).

How common is AMZ2 p.Ser55Pro (c.163T>C) in the general population?

AMZ2 p.Ser55Pro (c.163T>C) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about AMZ2 p.Ser55Pro (c.163T>C)?

AlphaMissense predicts likely pathogenic (score 0.792) — an in-silico prediction, not a clinical call.

AMZ2 p.Ser55Pro

c.163T>C · rs1555738665 · VCV3117488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.792 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.792	likely pathogenic
REVEL	0.189	benign-leaning
SaProt	LLR -8.39	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 4.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,778 bp · p 0.078 · regional, not allelic
Overall
CADD	25.9	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 0.0245% East Asian · 11/44,898 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000929% 15/1,614,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,082
South Asian	0.00439%	22,770

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.Ser55Pro
Coding: c.163T>C
MANE Select: NM_016627
dbSNP: rs1555738665
Type: single nucleotide variant
Location: chr17:68250350 (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.Ser55Phe Uncertain significance ★ ⚠ same residue
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.Arg284Pro 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-ser55pro (accessed [today's date]).

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