Is TXNRD2 p.Gly331= (c.993G>C) pathogenic?

TXNRD2 p.Gly331= (c.993G>C) is classified Likely benign in TXNRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-28). Very rare (popmax 0.000678%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Gly331= (c.993G>C)?

TXNRD2 p.Gly331= (c.993G>C) is associated with Cardiovascular phenotype, dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Gly331= (c.993G>C) in the general population?

TXNRD2 p.Gly331= (c.993G>C) is very rare (popmax 0.000678%, nfe) (gnomAD).

TXNRD2 p.Gly331=

c.993G>C · rs774604998 · VCV1583603

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000678%, 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 -0.45	GERP -2.9, phastCons 0.042
Overall
CADD	1.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,036 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,928 alleles · very rare

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.Gly331=
Coding: c.993G>C
MANE Select: NM_006440
dbSNP: rs774604998
Type: single nucleotide variant
Location: chr22:19883418 (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

Also linked: dilated cardiomyopathy

Similar variants

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.1182+5G>A Uncertain significance ★★ same condition
TXNRD2 c.1348-2A>G Uncertain significance ★★ same condition
TXNRD2 c.1348-9G>A Uncertain significance ★★ same condition
TXNRD2 c.1445+5G>C 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-gly331 (accessed [today's date]).

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