Is TNK2 p.Arg792Leu (c.2375G>T) pathogenic?

TNK2 p.Arg792Leu (c.2375G>T) is classified Uncertain significance in TNK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.088); No allele count reported in gnomAD v4.1 (AN 1,532,014).

How common is TNK2 p.Arg792Leu (c.2375G>T) in the general population?

TNK2 p.Arg792Leu (c.2375G>T) is no allele count reported in gnomAD v4.1 (AN 1,532,014) (gnomAD).

What do computational predictors say about TNK2 p.Arg792Leu (c.2375G>T)?

AlphaMissense predicts likely benign (score 0.088) — an in-silico prediction, not a clinical call.

TNK2 p.Arg792Leu

c.2375G>T · VCV4188070

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.088 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,532,014)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.088	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -6.68	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 0.39	GERP -2.6, phastCons 0.028
Regional constraint	o/e 1.27	unconstrained · MANE · 8,266 bp · p 7.5e-16 · regional, not allelic
Overall
CADD	18.54	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R777L vs ClinVar R792L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,532,014). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TNK2
Protein: p.Arg792Leu
Coding: c.2375G>T
MANE Select: NM_001382273
Type: single nucleotide variant
Location: chr3:195867923 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41 · 18 PDB
Residue 777 UniProt numbering: the 'disordered' region; the 'ebd domain' region

Full TNK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TNK2 p.Arg792Gln Uncertain significance ★ ⚠ same residue
TNK2 p.Arg792Trp Uncertain significance ★ ⚠ same residue
TNK2 c.1162-3C>T Uncertain significance ★★ same type
TNK2 c.-18-6750C>T Uncertain significance ★★ same type
TNK2 c.-18-6791C>G Uncertain significance ★★ same type
TNK2 c.-18-6794C>A Uncertain significance ★★ same type
TNK2 p.Ala147Thr Uncertain significance ★★ ⚠ same type
TNK2 p.Ala601Thr 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/tnk2-p-arg792leu (accessed [today's date]).

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