Is TXNRD2 p.Thr520= (c.1560A>C) pathogenic?

TXNRD2 p.Thr520= (c.1560A>C) is classified Likely benign in TXNRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). Very rare (popmax 8.55e-05%, nfe); Associated with dilated cardiomyopathy.

What condition is associated with TXNRD2 p.Thr520= (c.1560A>C)?

TXNRD2 p.Thr520= (c.1560A>C) is associated with dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Thr520= (c.1560A>C) in the general population?

TXNRD2 p.Thr520= (c.1560A>C) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

TXNRD2 p.Thr520=

c.1560A>C · rs763666305 · VCV1530002

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

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 -6.6	GERP -3
Overall
CADD	0.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.55e-05% European (non-Finnish) · 1/1,169,216 alleles

Overall 6.91e-05% 1/1,447,740 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: TXNRD2
Protein: p.Thr520=
Coding: c.1560A>C
MANE Select: NM_006440
dbSNP: rs763666305
Type: single nucleotide variant
Location: chr22:19877120 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Residue 520: a UniProt-annotated variant site (in gccd5; the mutant protein is undetectable in patient cells)

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.Thr520Arg Uncertain significance ★★ same residue
TXNRD2 p.Thr520Lys Uncertain significance ★ 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

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-thr520 (accessed [today's date]).

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