Is NOX3 p.Ser18Pro (c.52T>C) pathogenic?

NOX3 p.Ser18Pro (c.52T>C) is classified Uncertain significance in NOX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1981); Rare (popmax 0.169%, afr).

How common is NOX3 p.Ser18Pro (c.52T>C) in the general population?

NOX3 p.Ser18Pro (c.52T>C) is rare (popmax 0.169%, afr) (gnomAD).

What do computational predictors say about NOX3 p.Ser18Pro (c.52T>C)?

AlphaMissense predicts likely benign (score 0.1981) — an in-silico prediction, not a clinical call.

NOX3 p.Ser18Pro

c.52T>C · rs151011916 · VCV3201440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1981 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.169%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1981	likely benign
REVEL	0.465	indeterminate
SaProt	LLR -10.94	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	phastCons 0.008
Regional constraint	o/e 0.99	unconstrained · MANE · 59 kb · p 0.76 · regional, not allelic
Overall
CADD	13.57	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 0.169% African / African-American · 126/74,740 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.0124% 199/1,604,444 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.169%	593
Admixed American	0.0602%	1,661
Middle Eastern	0.0165%	6,074
Remaining individualsnot grpmax-eligible	0.00644%	15,538
European (non-Finnish)	0.00273%	36,626

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: NOX3
Protein: p.Ser18Pro
Coding: c.52T>C
MANE Select: NM_015718
dbSNP: rs151011916
Type: single nucleotide variant
Location: chr6:155455126 (GRCh38)
Gene constraint: LOEUF 1.2 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.84

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-ser18pro (accessed [today's date]).

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