Is TXNRD2 p.Ser411= (c.1233C>T) pathogenic?

TXNRD2 p.Ser411= (c.1233C>T) is classified Benign in TXNRD2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.15%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Ser411= (c.1233C>T)?

TXNRD2 p.Ser411= (c.1233C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Ser411= (c.1233C>T) in the general population?

TXNRD2 p.Ser411= (c.1233C>T) is low-frequency (popmax 3.15%, afr) (gnomAD).

TXNRD2 p.Ser411=

c.1233C>T · rs35099271 · VCV240654

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.15%, afr)

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 -12	GERP -3.4
Overall
CADD	0.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.15% African / African-American · 2,364/75,036 alleles

Filtering AF 3.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 3%

Overall 0.17% 2,738/1,613,714 alleles · low-frequency exomes 1,370/1,461,410 · genomes 1,368/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.15%	32
Remaining individualsnot grpmax-eligible	0.245%	408
Admixed American	0.22%	455
Middle Eastern	0.116%	866
South Asian	0.00878%	11,386
European (non-Finnish)	0.00627%	15,946

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.Ser411=
Coding: c.1233C>T
MANE Select: NM_006440
dbSNP: rs35099271
Type: single nucleotide variant
Location: chr22:19880221 (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-ser411 (accessed [today's date]).

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