Is DUOX2 p.Ala239Pro (c.715G>C) pathogenic?

DUOX2 p.Ala239Pro (c.715G>C) is classified Uncertain significance in DUOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-03). AlphaMissense: ambiguous (0.3401); Absent from gnomAD v4.1; Associated with DUOX2-related disorder.

What condition is associated with DUOX2 p.Ala239Pro (c.715G>C)?

DUOX2 p.Ala239Pro (c.715G>C) is associated with DUOX2-related disorder (ClinVar).

How common is DUOX2 p.Ala239Pro (c.715G>C) in the general population?

DUOX2 p.Ala239Pro (c.715G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUOX2 p.Ala239Pro (c.715G>C)?

AlphaMissense predicts ambiguous (score 0.3401) — an in-silico prediction, not a clinical call.

DUOX2 p.Ala239Pro

c.715G>C · rs758327952 · VCV2630559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3401 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

DUOX2-related disorder

Computational evidence

Protein change
AlphaMissense	0.3401	ambiguous
REVEL	0.566	indeterminate
SaProt	LLR -8.20	tolerated
Splicing
SpliceAI	Δ0.77	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.67	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,165 bp · p 0.98 · regional, not allelic
Overall
CADD	26.3	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: DUOX2
Protein: p.Ala239Pro
Coding: c.715G>C
MANE Select: NM_001363711
dbSNP: rs758327952
Type: single nucleotide variant
Location: chr15:45111384 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.37
Residue 239: 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

DUOX2-related disorder

Similar variants

DUOX2 p.Ala239Thr Uncertain significance ★★ ⚠ same residue
DUOX2 p.Ala239Asp Uncertain significance ★ ⚠ same residue
DUOX2 c.1040+1G>T Likely pathogenic ★★ same condition
DUOX2 p.Arg376Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
DUOX2 p.Arg701Ter Pathogenic/Likely pathogenic ★★ same condition
DUOX2 p.Cys703Ter Pathogenic/Likely pathogenic ★★ same condition
DUOX2 p.Gln1301Ter Pathogenic/Likely pathogenic ★★ same condition
DUOX2 p.Tyr425Ter Pathogenic ★★ 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-ala239pro (accessed [today's date]).

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