Is TXN2 p.Pro80Ser (c.238C>T) pathogenic?

TXN2 p.Pro80Ser (c.238C>T) is classified Uncertain significance in TXN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely pathogenic (0.9399); Absent from gnomAD v4.1.

How common is TXN2 p.Pro80Ser (c.238C>T) in the general population?

TXN2 p.Pro80Ser (c.238C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TXN2 p.Pro80Ser (c.238C>T)?

AlphaMissense predicts likely pathogenic (score 0.9399) — an in-silico prediction, not a clinical call.

TXN2 p.Pro80Ser

c.238C>T · rs2145828624 · VCV1362362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9399 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9399	likely pathogenic
REVEL	0.67	pathogenic-leaning
SaProt	LLR -11.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 13 kb · p 0.016 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: TXN2
Protein: p.Pro80Ser
Coding: c.238C>T
MANE Select: NM_012473
dbSNP: rs2145828624
Type: single nucleotide variant
Location: chr22:36480600 (GRCh38)
Gene constraint: LOEUF 1.358 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 3 PDB
Residue 80: the thioredoxin domain

Full TXN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TXN2 p.Ile126Val Uncertain significance ★★ ⚠ same type
TXN2 p.Ile165Thr Uncertain significance ★★ ⚠ same type
TXN2 p.Pro98Leu Uncertain significance ★★ ⚠ same type
TXN2 p.Ser29Cys Uncertain significance ★★ ⚠ same type
TXN2 c.387+30A>C Benign ★★ same type
TXN2 c.388-99C>A Benign ★★ same type
TXN2 p.Ala87= Likely benign ★★ same type
TXN2 p.Leu11= Benign ★★ same type

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/txn2-p-pro80ser (accessed [today's date]).

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