Is NOX5 p.Leu289Phe (c.865C>T) pathogenic?

NOX5 p.Leu289Phe (c.865C>T) is classified Uncertain significance in NOX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely pathogenic (0.6447); Absent from gnomAD v4.1.

How common is NOX5 p.Leu289Phe (c.865C>T) in the general population?

NOX5 p.Leu289Phe (c.865C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NOX5 p.Leu289Phe (c.865C>T)?

AlphaMissense predicts likely pathogenic (score 0.6447) — an in-silico prediction, not a clinical call.

NOX5 p.Leu289Phe

c.865C>T · rs2505239221 · VCV3201462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6447 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6447	likely pathogenic
REVEL	0.441	indeterminate
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.47	GERP -0.36, phastCons 0.92
Regional constraint	o/e 0.97	unconstrained · MANE · 42 kb · p 0.4 · regional, not allelic
Overall
CADD	13.21	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: NOX5
Protein: p.Leu289Phe
Coding: c.865C>T
MANE Select: NM_024505
dbSNP: rs2505239221
Type: single nucleotide variant
Location: chr15:69035363 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.89 · 5 PDB

Full NOX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NOX5 c.1899+7A>G Benign ★★ same type
NOX5 p.Arg759Gly Benign ★★ same type
NOX5 p.Trp300Ter Benign ★★ same type
NOX5 p.Ala172Glu Uncertain significance ★ ⚠ same type
NOX5 p.Ala256Val Uncertain significance ★ same type
NOX5 p.Ala285Val Uncertain significance ★ ⚠ same type
NOX5 p.Ala344Pro Uncertain significance ★ ⚠ same type
NOX5 p.Ala373Thr 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/nox5-p-leu289phe (accessed [today's date]).

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