Is TXNRD2 p.Asp359= (c.1077C>T) pathogenic?

TXNRD2 p.Asp359= (c.1077C>T) is classified Benign/Likely benign in TXNRD2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-16). Rare (popmax 0.78%, eas); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Asp359= (c.1077C>T)?

TXNRD2 p.Asp359= (c.1077C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Asp359= (c.1077C>T) in the general population?

TXNRD2 p.Asp359= (c.1077C>T) is rare (popmax 0.78%, eas) (gnomAD).

TXNRD2 p.Asp359=

c.1077C>T · rs147383232 · VCV414281

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.78%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.57 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.6	GERP -2.9
Overall
CADD	2.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.78% East Asian · 350/44,876 alleles

Filtering AF 0.713% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.686%

Overall 0.024% 388/1,613,730 alleles · rare exomes 343/1,461,376 · genomes 45/152,354 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.78%	128
Remaining individualsnot grpmax-eligible	0.016%	6,248
South Asian	0.0121%	8,280
European (non-Finnish)	0.00136%	73,748
African / African-American	0.00133%	75,060

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.Asp359=
Coding: c.1077C>T
MANE Select: NM_006440
dbSNP: rs147383232
Type: single nucleotide variant
Location: chr22:19883334 (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-asp359 (accessed [today's date]).

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