Is NOX1 p.Lys306Gln (c.916A>C) pathogenic?

NOX1 p.Lys306Gln (c.916A>C) is classified Uncertain significance in NOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely benign (0.094); Very rare (popmax 0.000341%, nfe).

How common is NOX1 p.Lys306Gln (c.916A>C) in the general population?

NOX1 p.Lys306Gln (c.916A>C) is very rare (popmax 0.000341%, nfe) (gnomAD).

What do computational predictors say about NOX1 p.Lys306Gln (c.916A>C)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

NOX1 p.Lys306Gln

c.916A>C · rs1390703729 · VCV3201430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000341%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.437	indeterminate
SaProt	LLR -5.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.3	GERP 0.72, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.36 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.000341% European (non-Finnish) · 3/880,933 alleles

Filtering AF 9.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000253% 3/1,188,013 alleles · very rare exomes 3/1,074,311 · genomes 0/113,702 · joint denominator

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: NOX1
Protein: p.Lys306Gln
Coding: c.916A>C
MANE Select: NM_007052
dbSNP: rs1390703729
Type: single nucleotide variant
Location: chrX:100850368 (GRCh38)
Structure: AlphaFold pLDDT 90.43
Residue 306: the fad-binding fr-type domain

Full NOX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NOX1 p.Arg241Cys Benign/Likely benign ★★ same type
NOX1 p.Arg356Ter Likely benign ★★ same type
NOX1 p.Arg378Lys Benign ★★ same type
NOX1 p.Met302Val Likely benign ★★ same type
NOX1 p.Met312Thr Likely benign ★★ same type
NOX1 p.Ser255= Benign ★★ same type
NOX1 c.672-5T>G Uncertain significance ★ same type
NOX1 c.898-1G>A 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/nox1-p-lys306gln (accessed [today's date]).

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