Is TXNRD2 p.Ala3Val (c.8C>T) pathogenic?

TXNRD2 p.Ala3Val (c.8C>T) is classified Uncertain significance in TXNRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-28). Very rare (popmax 8.68e-05%, nfe); Associated with dilated cardiomyopathy.

What condition is associated with TXNRD2 p.Ala3Val (c.8C>T)?

TXNRD2 p.Ala3Val (c.8C>T) is associated with dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Ala3Val (c.8C>T) in the general population?

TXNRD2 p.Ala3Val (c.8C>T) is very rare (popmax 8.68e-05%, nfe) (gnomAD).

TXNRD2 p.Ala3Val

c.8C>T · rs2517445051 · VCV2713883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.68e-05%, nfe)

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.128	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.45	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP 2.6	GERP 0.6, phastCons 0.97
Regional constraint	o/e 1.33	unconstrained · MANE · 101 bp · p 0.017 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.68e-05% European (non-Finnish) · 1/1,151,916 alleles

Overall 0.000145% 2/1,382,698 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0036%	27,756
European (non-Finnish)grpmax	8.68e-05%	1,151,916

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala3Val
Coding: c.8C>T
MANE Select: NM_000754 · reported on NM_006440
dbSNP: rs2517445051
Type: single nucleotide variant
Location: chr22:19941796 (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-ala3val (accessed [today's date]).

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