Is TNIK p.Ser574= (c.1722T>C) pathogenic?

TNIK p.Ser574= (c.1722T>C) is classified Likely benign in TNIK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-02-07). Ultra-rare (popmax 0.0776%, afr); Associated with TNIK-related disorder.

What condition is associated with TNIK p.Ser574= (c.1722T>C)?

TNIK p.Ser574= (c.1722T>C) is associated with TNIK-related disorder (ClinVar).

How common is TNIK p.Ser574= (c.1722T>C) in the general population?

TNIK p.Ser574= (c.1722T>C) is ultra-rare (popmax 0.0776%, afr) (gnomAD).

TNIK p.Ser574=

c.1722T>C · rs368677789 · VCV3051398

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0776%, afr)

Conditions

TNIK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.81, phastCons 1
Overall
CADD	9.595	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0776% African / African-American · 58/74,788 alleles

Filtering AF 0.0615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0558%

Overall 0.00372% 60/1,613,256 alleles · ultra-rare exomes 27/1,461,434 · genomes 33/151,822 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0776%	1,289
Remaining individualsnot grpmax-eligible	0.0032%	31,228

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: TNIK
Protein: p.Ser574=
Coding: c.1722T>C
MANE Select: NM_015028
dbSNP: rs368677789
Type: single nucleotide variant
Location: chr3:171128765 (GRCh38)
Gene constraint: LOEUF 0.338 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.60 · 12 PDB
Residue 574: the 'mediates interaction with nedd4' region; the 'disordered' region

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

Disease context

TNIK-related disorder

Similar variants

TNIK p.Arg1270Gln Uncertain significance ★ ⚠ same condition
TNIK c.949+3T>G Likely benign same condition
TNIK p.Arg632= Likely benign same condition
TNIK c.1609-14_1609-10dup Benign same condition
TNIK c.1609-17_1609-10dup Likely benign same condition
TNIK c.181-12_181-10del Likely benign same condition
TNIK p.Arg545Trp Uncertain significance ★★ ⚠ same type
TNIK p.Arg632Cys 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/tnik-p-ser574 (accessed [today's date]).

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