TXNRD2 p.Arg144Pro
c.431G>C · rs748674090 · VCV1318820
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00119%, nfe)
Conditions
1
dilated cardiomyopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.558 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 0.74, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 65 kb · p 0.0019 · regional, not allelic |
| Overall | ||
| CADD | 29.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00119%
European (non-Finnish) · 14/1,180,018 alleles
Filtering AF
0.000688%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.000867%
14/1,614,156 alleles · very rare
exomes 14/1,461,836 · genomes 0/152,320 · 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.Arg144Pro
- Coding
- c.431G>C
- MANE Select
- NM_006440
- dbSNP
- rs748674090
- Type
- single nucleotide variant
- Location
- chr22:19918161 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
Similar variants
- TXNRD2 p.Arg144Cys Uncertain significance ★★ same residue
- TXNRD2 p.Arg144His Uncertain significance ★★ same residue
- TXNRD2 p.Arg144Leu 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
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-arg144pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown