Is TXK p.Gly280Asp (c.839G>A) pathogenic?

TXK p.Gly280Asp (c.839G>A) is classified Uncertain significance in TXK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely pathogenic (0.9651); Absent from gnomAD v4.1.

How common is TXK p.Gly280Asp (c.839G>A) in the general population?

TXK p.Gly280Asp (c.839G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TXK p.Gly280Asp (c.839G>A)?

AlphaMissense predicts likely pathogenic (score 0.9651) — an in-silico prediction, not a clinical call.

TXK p.Gly280Asp

c.839G>A · VCV3464605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9651 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9651	likely pathogenic · top 6% in TXK
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -16.37	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 7.5	GERP 4.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 67 kb · p 0.023 · regional, not allelic
Overall
CADD	27.2	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: TXK
Protein: p.Gly280Asp
Coding: c.839G>A
MANE Select: NM_003328
Type: single nucleotide variant
Location: chr4:48086583 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.88 · 1 PDB
Residue 280: the protein kinase domain; a binding site

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

Similar variants

TXK p.Gly280Cys Uncertain significance ★ ⚠ same residue
TXK p.Ala160Val Uncertain significance ★ ⚠ same type
TXK p.Ala172Ser Uncertain significance ★ ⚠ same type
TXK p.Ala192Val Uncertain significance ★ ⚠ same type
TXK p.Ala491Thr Uncertain significance ★ ⚠ same type
TXK p.Ala514Val Uncertain significance ★ ⚠ same type
TXK p.Ala519Thr Uncertain significance ★ ⚠ same type
TXK p.Ala524Glu Uncertain significance ★ ⚠ 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/txk-p-gly280asp (accessed [today's date]).

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