Is TXK p.Pro507Thr (c.1519C>A) pathogenic?

TXK p.Pro507Thr (c.1519C>A) is classified Uncertain significance in TXK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.1857); Absent from gnomAD v4.1.

How common is TXK p.Pro507Thr (c.1519C>A) in the general population?

TXK p.Pro507Thr (c.1519C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TXK p.Pro507Thr (c.1519C>A)?

AlphaMissense predicts likely benign (score 0.1857) — an in-silico prediction, not a clinical call.

TXK p.Pro507Thr

c.1519C>A · VCV4194264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1857 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1857	likely benign
REVEL	0.714	pathogenic-leaning
SaProt	LLR -10.96	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 4.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 67 kb · p 0.023 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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.Pro507Thr
Coding: c.1519C>A
MANE Select: NM_003328
Type: single nucleotide variant
Location: chr4:48067702 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.88 · 1 PDB
Residue 507: the protein kinase domain

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

Similar variants

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
TXK p.Arg241His 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-pro507thr (accessed [today's date]).

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