Is TXNRD2 p.Val360fs (c.1077_1078insCATTG) pathogenic?

TXNRD2 p.Val360fs (c.10771078insCATTG) is classified Uncertain significance in TXNRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-02). Very rare (popmax 0.000254%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.Val360fs (c.1077_1078insCATTG)?

TXNRD2 p.Val360fs (c.1077_1078insCATTG) is associated with Cardiovascular phenotype (ClinVar).

How common is TXNRD2 p.Val360fs (c.1077_1078insCATTG) in the general population?

TXNRD2 p.Val360fs (c.1077_1078insCATTG) is very rare (popmax 0.000254%, nfe) (gnomAD).

TXNRD2 p.Val360fs

c.1077_1078insCATTG · rs2517282619 · VCV1785003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP 0.3, phastCons 0.5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,962 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,376 alleles · very rare

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.Val360fs
Coding: c.1077_1078insCATTG
MANE Select: NM_006440
dbSNP: rs2517282619
Type: Insertion
Location: chr22:19883333 (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

Similar variants

TXNRD2 p.Val360Met Uncertain significance ★★ same residue
TXNRD2 p.Val360= Likely benign ★ same residue
TXNRD2 p.Val360Leu Uncertain significance ★ same residue
TXNRD2 c.104-3C>G Uncertain significance ★★ same condition
TXNRD2 c.1182+5G>A Uncertain significance ★★ same condition
TXNRD2 c.172+3A>G Uncertain significance ★★ same condition
TXNRD2 c.450-1G>A Uncertain significance ★★ same condition
TXNRD2 c.528+2T>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-val360fs (accessed [today's date]).

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