Is TXNRD2 p.Val332= (c.996A>G) pathogenic?

TXNRD2 p.Val332= (c.996A>G) is classified Likely benign in TXNRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). Very rare (popmax 0.00288%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Val332= (c.996A>G)?

TXNRD2 p.Val332= (c.996A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is TXNRD2 p.Val332= (c.996A>G) in the general population?

TXNRD2 p.Val332= (c.996A>G) is very rare (popmax 0.00288%, nfe) (gnomAD).

TXNRD2 p.Val332=

c.996A>G · rs768796378 · VCV3225598

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -2.9
Overall
CADD	0.177	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00288% European (non-Finnish) · 34/1,180,036 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00211% 34/1,613,944 alleles · very rare exomes 32/1,461,706 · genomes 2/152,238 · 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.Val332=
Coding: c.996A>G
MANE Select: NM_006440
dbSNP: rs768796378
Type: single nucleotide variant
Location: chr22:19883415 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)

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

Similar variants

TXNRD2 c.104-3C>G Uncertain significance ★★ same condition
TXNRD2 c.1182+5G>A Uncertain significance ★★ same condition
TXNRD2 c.172+3A>G Uncertain significance ★★ same condition
TXNRD2 c.450-1G>A Uncertain significance ★★ same condition
TXNRD2 c.528+2T>C Uncertain significance ★★ same condition
TXNRD2 c.591+1G>A Uncertain significance ★★ same condition
TXNRD2 c.662+1G>A Uncertain significance ★★ same condition
TXNRD2 p.Ala131Gly 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-val332 (accessed [today's date]).

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