Is NOX5 p.Arg261Pro (c.782G>C) pathogenic?

NOX5 p.Arg261Pro (c.782G>C) is classified Uncertain significance in NOX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely benign (0.2274); Absent from gnomAD v4.1.

How common is NOX5 p.Arg261Pro (c.782G>C) in the general population?

NOX5 p.Arg261Pro (c.782G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NOX5 p.Arg261Pro (c.782G>C)?

AlphaMissense predicts likely benign (score 0.2274) — an in-silico prediction, not a clinical call.

NOX5 p.Arg261Pro

c.782G>C · VCV3921191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2274 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,648)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2274	likely benign
REVEL	0.417	indeterminate
SaProt	LLR -13.47	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 -0.26	GERP -0.58
Regional constraint	o/e 0.97	unconstrained · MANE · 42 kb · p 0.4 · regional, not allelic
Overall
CADD	11.92	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

No allele count reported in gnomAD v4.1 (AN 1,596,648). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NOX5
Protein: p.Arg261Pro
Coding: c.782G>C
MANE Select: NM_024505
Type: single nucleotide variant
Location: chr15:69033204 (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-arg261pro (accessed [today's date]).

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