Is TXNRD2 p.Val71Met (c.211G>A) pathogenic?

TXNRD2 p.Val71Met (c.211G>A) is classified Uncertain significance in TXNRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-06). Very rare (popmax 0.00958%, amr); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Val71Met (c.211G>A)?

TXNRD2 p.Val71Met (c.211G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy (ClinVar).

How common is TXNRD2 p.Val71Met (c.211G>A) in the general population?

TXNRD2 p.Val71Met (c.211G>A) is very rare (popmax 0.00958%, amr) (gnomAD).

TXNRD2 p.Val71Met

c.211G>A · rs867369272 · VCV2138928

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00958%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.489	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 65 kb · p 0.0019 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00958% Admixed American · 5/52,186 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.00064% 10/1,563,088 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00958%	10,437
African / African-American	0.00272%	36,742
Finnishnot grpmax-eligible	0.00165%	60,728
European (non-Finnish)	0.000173%	577,277

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.Val71Met
Coding: c.211G>A
MANE Select: NM_006440
dbSNP: rs867369272
Type: single nucleotide variant
Location: chr22:19919561 (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-val71met (accessed [today's date]).

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