Is TXNRD2 p.Pro402= (c.1206G>A) pathogenic?

TXNRD2 p.Pro402= (c.1206G>A) is classified Benign in TXNRD2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 55.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with dilated cardiomyopathy.

What condition is associated with TXNRD2 p.Pro402= (c.1206G>A)?

TXNRD2 p.Pro402= (c.1206G>A) is associated with dilated cardiomyopathy (ClinVar).

TXNRD2 p.Pro402=

Q: How common is TXNRD2 p.Pro402= (c.1206G>A) in the general population?

TXNRD2 p.Pro402= (c.1206G>A) is common (popmax 55.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1206G>A · rs1139795 · VCV263385

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 55.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

dilated cardiomyopathy

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 -14	GERP -3.4
Overall
CADD	0.225	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 55.9% African / African-American · 41,907/74,922 alleles

Filtering AF 55.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 55.3%

Overall 17.4% 280,359/1,613,250 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	55.9%	2
Middle Eastern	25.1%	4
Ashkenazi Jewishnot grpmax-eligible	21.1%	5
South Asian	19.2%	5
Remaining individualsnot grpmax-eligible	18.7%	5
Admixed American	16.6%	6
European (non-Finnish)	15.6%	6
Amishnot grpmax-eligible	15.3%	7
Finnishnot grpmax-eligible	9.07%	11
East Asian	4.12%	24

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.Pro402=
Coding: c.1206G>A
MANE Select: NM_006440
dbSNP: rs1139795
Type: single nucleotide variant
Location: chr22:19880248 (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

dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TXNRD2 p.Pro402Leu 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
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-pro402 (accessed [today's date]).

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