Is TXNRD2 p.Ala7Val (c.20C>T) pathogenic?

TXNRD2 p.Ala7Val (c.20C>T) is classified Uncertain significance in TXNRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-15). Very rare (popmax 0.000174%, nfe); Associated with dilated cardiomyopathy.

What condition is associated with TXNRD2 p.Ala7Val (c.20C>T)?

TXNRD2 p.Ala7Val (c.20C>T) is associated with dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Ala7Val (c.20C>T) in the general population?

TXNRD2 p.Ala7Val (c.20C>T) is very rare (popmax 0.000174%, nfe) (gnomAD).

TXNRD2 p.Ala7Val

c.20C>T · rs1230683925 · VCV1785878

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Conditions

dilated cardiomyopathy

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.17	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.45	GERP -0.54, phastCons 0.004
Regional constraint	o/e 1.33	unconstrained · MANE · 101 bp · p 0.017 · regional, not allelic
Overall
CADD	18.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,148,078 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000131% 2/1,528,418 alleles · very rare exomes 2/1,376,192 · genomes 0/152,226 · 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: TXNRD2
Protein: p.Ala7Val
Coding: c.20C>T
MANE Select: NM_006440
dbSNP: rs1230683925
Type: single nucleotide variant
Location: chr22:19941784 (GRCh38)

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

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-ala7val (accessed [today's date]).

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