Is DUOX2 p.Val289Phe (c.865G>T) pathogenic?

DUOX2 p.Val289Phe (c.865G>T) is classified Uncertain significance in DUOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.7435); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DUOX2 p.Val289Phe (c.865G>T)?

DUOX2 p.Val289Phe (c.865G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DUOX2 p.Val289Phe (c.865G>T) in the general population?

DUOX2 p.Val289Phe (c.865G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUOX2 p.Val289Phe (c.865G>T)?

AlphaMissense predicts likely pathogenic (score 0.7435) — an in-silico prediction, not a clinical call.

DUOX2 p.Val289Phe

c.865G>T · VCV4834071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7435 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7435	likely pathogenic
REVEL	0.939	strongly pathogenic-leaning
SaProt	LLR -12.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.26	constrained · MANE · 126 bp · p 1.7e-08 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

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

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: DUOX2
Protein: p.Val289Phe
Coding: c.865G>T
MANE Select: NM_001363711
Type: single nucleotide variant
Location: chr15:45111128 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.37
Residue 289: the 'peroxidase-like; mediates peroxidase activity' region; a disulfide bond

Full DUOX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DUOX2 c.513+1G>C Pathogenic/Likely pathogenic ★★ same condition
DUOX2 p.Arg434Ter Pathogenic ★★ same condition
DUOX2 p.Arg625Ter Pathogenic/Likely pathogenic ★★ same condition
DUOX2 c.3693+5G>C Uncertain significance ★★ same condition
DUOX2 p.Ala1133Pro Uncertain significance ★★ ⚠ same condition
DUOX2 p.Ala1138Thr Uncertain significance ★★ ⚠ same condition
DUOX2 p.Ala1230Ser Uncertain significance ★★ ⚠ same condition
DUOX2 p.Ala1306Thr Uncertain significance ★★ ⚠ same condition

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/duox2-p-val289phe (accessed [today's date]).

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