Is TXNRD2 p.Glu362= (c.1086G>A) pathogenic?

TXNRD2 p.Glu362= (c.1086G>A) is classified Uncertain significance in TXNRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). Very rare (popmax 0.000509%, nfe); Associated with dilated cardiomyopathy.

What condition is associated with TXNRD2 p.Glu362= (c.1086G>A)?

TXNRD2 p.Glu362= (c.1086G>A) is associated with dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Glu362= (c.1086G>A) in the general population?

TXNRD2 p.Glu362= (c.1086G>A) is very rare (popmax 0.000509%, nfe) (gnomAD).

TXNRD2 p.Glu362=

c.1086G>A · VCV4706551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

dilated cardiomyopathy

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 · C>G here scores Δ0.36 · evaluated, not missing
Pangolin	Δ0.47	loss · gain 0.03 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 5.8	GERP 0.067, phastCons 1
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,930 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,461,174 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.Glu362=
Coding: c.1086G>A
MANE Select: NM_006440
Type: single nucleotide variant
Location: chr22:19883325 (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 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
TXNRD2 c.172+3A>G 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-glu362 (accessed [today's date]).

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