Is TXNRD2 p.Arg9Pro (c.26G>C) pathogenic?

TXNRD2 p.Arg9Pro (c.26G>C) is classified Uncertain significance in TXNRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). Very rare (popmax 0.00122%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Arg9Pro (c.26G>C)?

TXNRD2 p.Arg9Pro (c.26G>C) is associated with Cardiovascular phenotype, dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Arg9Pro (c.26G>C) in the general population?

TXNRD2 p.Arg9Pro (c.26G>C) is very rare (popmax 0.00122%, nfe) (gnomAD).

TXNRD2 p.Arg9Pro

c.26G>C · rs866665461 · VCV1794907

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00122%, nfe)

Conditions

Cardiovascular phenotype

⚠ 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	0.219	benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.62	GERP -0.61
Regional constraint	o/e 1.33	unconstrained · MANE · 101 bp · p 0.017 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00122% European (non-Finnish) · 14/1,147,386 alleles

Filtering AF 0.000708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000554%

Overall 0.000917% 14/1,527,462 alleles · very rare exomes 13/1,375,296 · genomes 1/152,166 · 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.Arg9Pro
Coding: c.26G>C
MANE Select: NM_006440
dbSNP: rs866665461
Type: single nucleotide variant
Location: chr22:19941778 (GRCh38)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy

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-arg9pro (accessed [today's date]).

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