Is TNK2 p.Pro599Ser (c.1795C>T) pathogenic?

TNK2 p.Pro599Ser (c.1795C>T) is classified Benign in TNK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-13). AlphaMissense: likely benign (0.0777); Low-frequency (popmax 3.41%, afr).

How common is TNK2 p.Pro599Ser (c.1795C>T) in the general population?

TNK2 p.Pro599Ser (c.1795C>T) is low-frequency (popmax 3.41%, afr) (gnomAD).

What do computational predictors say about TNK2 p.Pro599Ser (c.1795C>T)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

TNK2 p.Pro599Ser

c.1795C>T · rs201643400 · VCV1572547

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.41%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -7.88	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 8.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 8,266 bp · p 7.5e-16 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P584S vs ClinVar P599S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.41% African / African-American · 2,497/73,166 alleles

Filtering AF 3.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.26%

Overall 0.184% 2,852/1,553,188 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.41%	29
Admixed American	0.298%	335
Remaining individualsnot grpmax-eligible	0.277%	361
South Asian	0.00578%	17,310
European (non-Finnish)	0.00302%	33,120
Finnishnot grpmax-eligible	0.00212%	47,142

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: TNK2
Protein: p.Pro599Ser
Coding: c.1795C>T
MANE Select: NM_001382273
dbSNP: rs201643400
Type: single nucleotide variant
Location: chr3:195868503 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41 · 18 PDB

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

Similar variants

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
TNK2 p.Ala641Thr Uncertain significance ★★ ⚠ same type
TNK2 p.Ala676Thr 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-pro599ser (accessed [today's date]).

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