Is DUOX2 p.Ser1237fs (c.3708del) pathogenic?

DUOX2 p.Ser1237fs (c.3708del) is classified Pathogenic in DUOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Very rare (popmax 0.00133%, afr).

How common is DUOX2 p.Ser1237fs (c.3708del) in the general population?

DUOX2 p.Ser1237fs (c.3708del) is very rare (popmax 0.00133%, afr) (gnomAD).

DUOX2 p.Ser1237fs

c.3708del · VCV4809068

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 29 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,068 alleles

Overall 6.84e-05% 1/1,461,882 alleles · very rare

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: DUOX2
Protein: p.Ser1237fs
Coding: c.3708del
MANE Select: NM_001363711
Type: Deletion
Location: chr15:45097377 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.37
Residue 1237: the ferric oxidoreductase domain; the 'interaction with txndc11' region

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

Similar variants

DUOX2 p.Ser1237_Tyr1238insSer Conflicting classifications of pathogenicity ★ same residue
DUOX2 c.3516_3531del Pathogenic ★★ same type
DUOX2 p.Ala1004fs Likely pathogenic ★★ same type
DUOX2 p.Gln202fs Pathogenic/Likely pathogenic ★★ same type
DUOX2 p.Gln466fs Pathogenic/Likely pathogenic ★★ same type
DUOX2 p.Glu127fs Pathogenic/Likely pathogenic ★★ same type
DUOX2 p.Glu160fs Pathogenic ★★ same type
DUOX2 p.Gly1386fs Pathogenic/Likely pathogenic ★★ 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/duox2-p-ser1237fs (accessed [today's date]).

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