Is TXNRD2 p.Arg286= (c.858G>A) pathogenic?

TXNRD2 p.Arg286= (c.858G>A) is classified Likely benign in TXNRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-27). Ultra-rare (popmax 0.0379%, eas); Associated with dilated cardiomyopathy.

What condition is associated with TXNRD2 p.Arg286= (c.858G>A)?

TXNRD2 p.Arg286= (c.858G>A) is associated with dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Arg286= (c.858G>A) in the general population?

TXNRD2 p.Arg286= (c.858G>A) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

TXNRD2 p.Arg286=

c.858G>A · rs201503021 · VCV700080

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Conditions

dilated cardiomyopathy

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 -0.045	GERP -1.2, phastCons 0.001
Overall
CADD	2.087	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0379% East Asian · 17/44,884 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00124% 20/1,613,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,640
Remaining individualsnot grpmax-eligible	0.0032%	31,253
European (non-Finnish)	8.47e-05%	1,180,032

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: TXNRD2
Protein: p.Arg286=
Coding: c.858G>A
MANE Select: NM_006440
dbSNP: rs201503021
Type: single nucleotide variant
Location: chr22:19895498 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)

Full TXNRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TXNRD2 p.Arg286Ser Conflicting classifications of pathogenicity ★ same residue
TXNRD2 c.104-1G>A Uncertain significance ★★ same condition
TXNRD2 c.104-3C>G Uncertain significance ★★ same condition
TXNRD2 c.1086+4C>T Uncertain significance ★★ same condition
TXNRD2 c.1087-2A>G Uncertain significance ★★ same condition
TXNRD2 c.1348-2A>G Uncertain significance ★★ same condition
TXNRD2 c.1348-9G>A Uncertain significance ★★ same condition
TXNRD2 c.1445+5G>C Uncertain significance ★★ 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/txnrd2-p-arg286 (accessed [today's date]).

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