Is TXNRD2 p.Phe383= (c.1149C>T) pathogenic?

TXNRD2 p.Phe383= (c.1149C>T) is classified Likely benign in TXNRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-09-27). Ultra-rare (popmax 0.0111%, eas); Associated with dilated cardiomyopathy.

What condition is associated with TXNRD2 p.Phe383= (c.1149C>T)?

TXNRD2 p.Phe383= (c.1149C>T) is associated with dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Phe383= (c.1149C>T) in the general population?

TXNRD2 p.Phe383= (c.1149C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

TXNRD2 p.Phe383=

c.1149C>T · rs768999643 · VCV524927

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

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 -10	GERP -2.7
Overall
CADD	0.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,898 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00663% 107/1,613,314 alleles · ultra-rare exomes 99/1,461,098 · genomes 8/152,216 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,980
South Asian	0.00878%	11,386
European (non-Finnish)	0.0072%	13,883
Admixed American	0.005%	20,003
Remaining individualsnot grpmax-eligible	0.0048%	20,825
African / African-American	0.00267%	37,465
Finnishnot grpmax-eligible	0.00158%	63,278

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.Phe383=
Coding: c.1149C>T
MANE Select: NM_006440
dbSNP: rs768999643
Type: single nucleotide variant
Location: chr22:19880655 (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 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
TXNRD2 c.172+3A>G 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-phe383 (accessed [today's date]).

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