Is TXNRD2 p.Pro122= (c.366G>A) pathogenic?

TXNRD2 p.Pro122= (c.366G>A) is classified Likely benign in TXNRD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-05). Very rare (popmax 0.00446%, eas); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Pro122= (c.366G>A)?

TXNRD2 p.Pro122= (c.366G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Pro122= (c.366G>A) in the general population?

TXNRD2 p.Pro122= (c.366G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

TXNRD2 p.Pro122=

c.366G>A · rs3747068 · VCV1149689

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 -9.3	GERP -3
Overall
CADD	1.225	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,816 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000684% 11/1,608,234 alleles · very rare exomes 9/1,456,298 · genomes 2/151,936 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,408
South Asian	0.00439%	22,770
African / African-American	0.00267%	37,467
Finnishnot grpmax-eligible	0.00171%	58,616
European (non-Finnish)	0.00017%	589,904

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.Pro122=
Coding: c.366G>A
MANE Select: NM_006440
dbSNP: rs3747068
Type: single nucleotide variant
Location: chr22:19918868 (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 p.Pro122Leu Uncertain significance ★★ same residue
TXNRD2 p.Pro122Ala Uncertain significance ★ same residue
TXNRD2 p.Pro122Ser Uncertain significance ★ same residue
TXNRD2 p.Pro122Thr 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

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-pro122 (accessed [today's date]).

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