Is DUOX2 p.Arg101= (c.303C>A) pathogenic?

DUOX2 p.Arg101= (c.303C>A) is classified Benign/Likely benign in DUOX2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-12). Low-frequency (popmax 4.07%, eas); Associated with thyroid dyshormonogenesis 6.

What condition is associated with DUOX2 p.Arg101= (c.303C>A)?

DUOX2 p.Arg101= (c.303C>A) is associated with thyroid dyshormonogenesis 6 (ClinVar).

How common is DUOX2 p.Arg101= (c.303C>A) in the general population?

DUOX2 p.Arg101= (c.303C>A) is low-frequency (popmax 4.07%, eas) (gnomAD).

How is Genetic transient congenital hypothyroidism inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DUOX2 p.Arg101=

c.303C>A · rs117041393 · VCV773048

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.07%, eas)

Conditions

thyroid dyshormonogenesis 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.62 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP -0.38, phastCons 1
Overall
CADD	15.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.07% East Asian · 1,825/44,854 alleles

Filtering AF 3.91% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.85%

Overall 0.132% 2,136/1,613,144 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	4.07%	25
Remaining individualsnot grpmax-eligible	0.375%	267
Admixed American	0.055%	1,818
South Asian	0.0264%	3,795
African / African-American	0.0133%	7,503
European (non-Finnish)	0.000848%	117,977

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.Arg101=
Coding: c.303C>A
MANE Select: NM_001363711
dbSNP: rs117041393
Type: single nucleotide variant
Location: chr15:45112576 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.37
Residue 101: the 'peroxidase-like; mediates peroxidase activity' region

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

Disease context

thyroid dyshormonogenesis 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Genetic transient congenital hypothyroidism (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DUOX2 p.Arg101Cys Uncertain significance ★ ⚠ same residue
DUOX2 p.Arg101Leu Uncertain significance ★ ⚠ same residue
DUOX2 c.1831+2T>G Likely pathogenic ★★ same condition
DUOX2 c.2335-1G>C Pathogenic/Likely pathogenic ★★ same condition
DUOX2 c.2560+2T>C Likely pathogenic ★★ same condition
DUOX2 c.3006-2A>G Likely pathogenic ★★ same condition
DUOX2 c.3693+1G>T Pathogenic/Likely pathogenic ★★ same condition
DUOX2 c.4081-1G>A Likely 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-arg101 (accessed [today's date]).

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