Is TXNRD2 p.Ala2Val (c.5C>T) pathogenic?

TXNRD2 p.Ala2Val (c.5C>T) is classified Uncertain significance in TXNRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). Very rare (popmax 0.000174%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Ala2Val (c.5C>T)?

TXNRD2 p.Ala2Val (c.5C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is TXNRD2 p.Ala2Val (c.5C>T) in the general population?

TXNRD2 p.Ala2Val (c.5C>T) is very rare (popmax 0.000174%, nfe) (gnomAD).

TXNRD2 p.Ala2Val

c.5C>T · rs2517445068 · VCV3225595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000174%, 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	0.191	benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.6	GERP -0.5, phastCons 0.96
Regional constraint	o/e 1.33	unconstrained · MANE · 101 bp · p 0.017 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,151,666 alleles

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

Overall 0.000195% 3/1,534,672 alleles · very rare exomes 3/1,382,376 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00217%	46,010
European (non-Finnish)grpmax	0.000174%	575,835

Finnish 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.Ala2Val
Coding: c.5C>T
MANE Select: NM_006440
dbSNP: rs2517445068
Type: single nucleotide variant
Location: chr22:19941799 (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

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-ala2val (accessed [today's date]).

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