Is DUOXA2 p.Arg274Pro (c.821G>C) pathogenic?

DUOXA2 p.Arg274Pro (c.821G>C) is classified Uncertain significance in DUOXA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). AlphaMissense: likely benign (0.2513); Very rare (popmax 0.00119%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DUOXA2 p.Arg274Pro (c.821G>C)?

DUOXA2 p.Arg274Pro (c.821G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DUOXA2 p.Arg274Pro (c.821G>C) in the general population?

DUOXA2 p.Arg274Pro (c.821G>C) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about DUOXA2 p.Arg274Pro (c.821G>C)?

AlphaMissense predicts likely benign (score 0.2513) — an in-silico prediction, not a clinical call.

DUOXA2 p.Arg274Pro

c.821G>C · rs750438741 · VCV3086193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2513 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2513	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -14.73	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	GERP -2, phastCons 0.026
Regional constraint	o/e 1.15	unconstrained · MANE · 3,300 bp · p 0.0029 · regional, not allelic
Overall
CADD	13.65	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

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,876 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000868% 14/1,613,772 alleles · very rare exomes 14/1,461,426 · genomes 0/152,346 · joint denominator

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: DUOXA2
Protein: p.Arg274Pro
Coding: c.821G>C
MANE Select: NM_207581
dbSNP: rs750438741
Type: single nucleotide variant
Location: chr15:45117767 (GRCh38)

Full DUOXA2 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

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/duoxa2-p-arg274pro (accessed [today's date]).

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