Is DUOX2 p.Phe211= (c.633C>T) pathogenic?

DUOX2 p.Phe211= (c.633C>T) is classified Conflicting classifications of pathogenicity in DUOX2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-05). Rare (popmax 0.699%, afr); Associated with thyroid dyshormonogenesis 6.

What condition is associated with DUOX2 p.Phe211= (c.633C>T)?

DUOX2 p.Phe211= (c.633C>T) is associated with thyroid dyshormonogenesis 6 (ClinVar).

How common is DUOX2 p.Phe211= (c.633C>T) in the general population?

DUOX2 p.Phe211= (c.633C>T) is rare (popmax 0.699%, afr) (gnomAD).

How is Genetic transient congenital hypothyroidism inherited?

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

DUOX2 p.Phe211=

c.633C>T · rs35157799 · VCV316181

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.699%, afr)

Conditions

thyroid dyshormonogenesis 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.74	GERP -0.31, phastCons 1
Overall
CADD	5.899	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.699% African / African-American · 506/72,350 alleles

Filtering AF 0.649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.629%

Overall 0.106% 1,637/1,549,276 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.699%	143
Admixed American	0.16%	626
Remaining individualsnot grpmax-eligible	0.112%	895
European (non-Finnish)	0.0787%	1,271
Finnishnot grpmax-eligible	0.0527%	1,897
Middle Eastern	0.0459%	2,178
East Asian	0.043%	2,326
South Asian	0.0297%	3,369
Ashkenazi Jewishnot grpmax-eligible	0.0106%	9,419

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.Phe211=
Coding: c.633C>T
MANE Select: NM_001363711
dbSNP: rs35157799
Type: single nucleotide variant
Location: chr15:45111466 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.37
Residue 211: 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

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 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
DUOX2 c.4239+1G>A Likely pathogenic ★★ same condition
DUOX2 c.513+1G>C Pathogenic/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-phe211 (accessed [today's date]).

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