Is NOX3 p.Ser57Pro (c.169T>C) pathogenic?

NOX3 p.Ser57Pro (c.169T>C) is classified Uncertain significance in NOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: ambiguous (0.5434); Absent from gnomAD v4.1.

How common is NOX3 p.Ser57Pro (c.169T>C) in the general population?

NOX3 p.Ser57Pro (c.169T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NOX3 p.Ser57Pro (c.169T>C)?

AlphaMissense predicts ambiguous (score 0.5434) — an in-silico prediction, not a clinical call.

NOX3 p.Ser57Pro

c.169T>C · VCV3300530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5434 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5434	ambiguous
REVEL	0.521	indeterminate
SaProt	LLR -10.41	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 59 kb · p 0.76 · regional, not allelic
Overall
CADD	19.62	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: NOX3
Protein: p.Ser57Pro
Coding: c.169T>C
MANE Select: NM_015718
Type: single nucleotide variant
Location: chr6:155454897 (GRCh38)
Gene constraint: LOEUF 1.2 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.84
Residue 57: the ferric oxidoreductase domain

Full NOX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NOX3 p.Ala106Thr Uncertain significance ★ ⚠ same type
NOX3 p.Ala119Glu Uncertain significance ★ ⚠ same type
NOX3 p.Ala141Thr Uncertain significance ★ ⚠ same type
NOX3 p.Ala247Glu Uncertain significance ★ ⚠ same type
NOX3 p.Ala318Val Uncertain significance ★ ⚠ same type
NOX3 p.Ala343Val Uncertain significance ★ ⚠ same type
NOX3 p.Ala361Thr Uncertain significance ★ ⚠ same type
NOX3 p.Ala407Thr 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/nox3-p-ser57pro (accessed [today's date]).

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