Is TXN2 p.Pro98= (c.294G>A) pathogenic?

TXN2 p.Pro98= (c.294G>A) is classified Benign/Likely benign in TXN2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.7%, mid); Associated with combined oxidative phosphorylation deficiency 29.

What condition is associated with TXN2 p.Pro98= (c.294G>A)?

TXN2 p.Pro98= (c.294G>A) is associated with combined oxidative phosphorylation deficiency 29 (ClinVar).

How common is TXN2 p.Pro98= (c.294G>A) in the general population?

TXN2 p.Pro98= (c.294G>A) is low-frequency (popmax 1.7%, mid) (gnomAD).

TXN2 p.Pro98=

Q: How is Combined oxidative phosphorylation defect type 29 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.294G>A · rs150502647 · VCV774540

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.7%, mid)

Conditions

combined oxidative phosphorylation deficiency 29

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 -5.2	GERP -3.2
Overall
CADD	2.955	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.7% Middle Eastern · 103/6,062 alleles

Filtering AF 1.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.33%

Overall 0.742% 11,979/1,614,164 alleles · low-frequency exomes 11,088/1,461,888 · genomes 891/152,276 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.7%	59
Ashkenazi Jewishnot grpmax-eligible	1.54%	65
European (non-Finnish)	0.843%	119
Remaining individualsnot grpmax-eligible	0.776%	129
Admixed American	0.613%	163
South Asian	0.345%	290
Finnishnot grpmax-eligible	0.315%	317
African / African-American	0.139%	721

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: TXN2
Protein: p.Pro98=
Coding: c.294G>A
MANE Select: NM_012473
dbSNP: rs150502647
Type: single nucleotide variant
Location: chr22:36476826 (GRCh38)
Gene constraint: LOEUF 1.358 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 3 PDB
Residue 98: an α-helix; the thioredoxin domain

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

Disease context

combined oxidative phosphorylation deficiency 29 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined oxidative phosphorylation defect type 29 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

TXN2 p.Pro98Leu Uncertain significance ★★ ⚠ same residue
TXN2 p.Ile126Val Uncertain significance ★★ ⚠ same condition
TXN2 c.387+30A>C Benign ★★ same condition
TXN2 p.Trp24Ter Pathogenic same condition
TXN2 p.Ile165Thr Uncertain significance ★★ ⚠ same type
TXN2 p.Ser29Cys Uncertain significance ★★ ⚠ same type
TXN2 c.388-99C>A Benign ★★ same type
TXN2 p.Ala87= Likely 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-pro98 (accessed [today's date]).

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