Is AMZ1 p.Phe55Leu (c.163T>C) pathogenic?

AMZ1 p.Phe55Leu (c.163T>C) is classified Uncertain significance in AMZ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely pathogenic (0.9859); Absent from gnomAD v4.1.

How common is AMZ1 p.Phe55Leu (c.163T>C) in the general population?

AMZ1 p.Phe55Leu (c.163T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMZ1 p.Phe55Leu (c.163T>C)?

AlphaMissense predicts likely pathogenic (score 0.9859) — an in-silico prediction, not a clinical call.

AMZ1 p.Phe55Leu

c.163T>C · VCV4048429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9859 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9859	likely pathogenic · top 1% in AMZ1
REVEL	0.391	indeterminate
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.53	unconstrained · MANE · 12 kb · p 2.2e-43 · regional, not allelic
Overall
CADD	24.0	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

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: AMZ1
Protein: p.Phe55Leu
Coding: c.163T>C
MANE Select: NM_001384743
Type: single nucleotide variant
Location: chr7:2700614 (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.Phe55Ser Uncertain significance ★ ⚠ same residue
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

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-phe55leu (accessed [today's date]).

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