Is TXNRD2 p.His419Pro (c.1256A>C) pathogenic?

TXNRD2 p.His419Pro (c.1256A>C) is classified Uncertain significance in TXNRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-04). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with TXNRD2 p.His419Pro (c.1256A>C)?

TXNRD2 p.His419Pro (c.1256A>C) is associated with Cardiovascular phenotype (ClinVar).

How common is TXNRD2 p.His419Pro (c.1256A>C) in the general population?

TXNRD2 p.His419Pro (c.1256A>C) is absent from gnomAD v4.1 (gnomAD).

TXNRD2 p.His419Pro

c.1256A>C · rs2517274854 · VCV1761827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.693	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 65 kb · p 0.0019 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TXNRD2
Protein: p.His419Pro
Coding: c.1256A>C
MANE Select: NM_006440
dbSNP: rs2517274854
Type: single nucleotide variant
Location: chr22:19880198 (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.His419= Likely benign ★★ 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
TXNRD2 c.591+1G>A Uncertain significance ★★ same condition
TXNRD2 c.662+1G>A 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-his419pro (accessed [today's date]).

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