Is TXK p.Lys320Arg (c.959A>G) pathogenic?

TXK p.Lys320Arg (c.959A>G) is classified Uncertain significance in TXK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely benign (0.0684); Very rare (popmax 0.00534%, afr).

How common is TXK p.Lys320Arg (c.959A>G) in the general population?

TXK p.Lys320Arg (c.959A>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about TXK p.Lys320Arg (c.959A>G)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

TXK p.Lys320Arg

c.959A>G · rs891932684 · VCV2264700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.39, phastCons 0.9
Regional constraint	o/e 0.91	unconstrained · MANE · 67 kb · p 0.023 · regional, not allelic
Overall
CADD	13.44	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00534% African / African-American · 4/74,892 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000559% 9/1,611,262 alleles · very rare exomes 7/1,459,042 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,723
European (non-Finnish)	0.000425%	235,517

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: TXK
Protein: p.Lys320Arg
Coding: c.959A>G
MANE Select: NM_003328
dbSNP: rs891932684
Type: single nucleotide variant
Location: chr4:48080126 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.88 · 1 PDB
Residue 320: the protein kinase domain

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

Similar variants

TXK p.Lys320Gln 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-lys320arg (accessed [today's date]).

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