Is DSTYK p.Arg790Cys (c.2368C>T) pathogenic?

DSTYK p.Arg790Cys (c.2368C>T) is classified Uncertain significance in DSTYK (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.2123); Very rare (popmax 0.0022%, sas); Associated with congenital anomalies of kidney and urinary tract 1.

What condition is associated with DSTYK p.Arg790Cys (c.2368C>T)?

DSTYK p.Arg790Cys (c.2368C>T) is associated with congenital anomalies of kidney and urinary tract 1 (ClinVar).

How common is DSTYK p.Arg790Cys (c.2368C>T) in the general population?

DSTYK p.Arg790Cys (c.2368C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about DSTYK p.Arg790Cys (c.2368C>T)?

AlphaMissense predicts likely benign (score 0.2123) — an in-silico prediction, not a clinical call.

DSTYK p.Arg790Cys

c.2368C>T · rs773130126 · VCV224359

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital anomalies of kidney and urinary tract 1

Computational evidence

Protein change
AlphaMissense	0.2123	likely benign
REVEL	0.533	indeterminate
SaProt	LLR -9.03	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 9,607 bp · p 6.4e-10 · regional, not allelic
Overall
CADD	33.0	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 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.0013% 21/1,613,934 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,541
European (non-Finnish)	0.00161%	62,104

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: DSTYK
Protein: p.Arg790Cys
Coding: c.2368C>T
MANE Select: NM_015375
dbSNP: rs773130126
Type: single nucleotide variant
Location: chr1:205150779 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 790: the protein kinase domain; a UniProt-annotated variant site (in cakut1; uncertain significance)

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

Disease context

congenital anomalies of kidney and urinary tract 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DSTYK p.Arg790His Uncertain significance ★ ⚠ same residue
DSTYK p.Arg626Gln Uncertain significance ★★ ⚠ same condition
DSTYK p.Gly32Asp Uncertain significance ★★ ⚠ same condition
DSTYK p.Cys641Arg Benign ★★ same condition
DSTYK p.Phe676= Benign ★★ same condition
DSTYK p.Gln465Arg Likely pathogenic ★ ⚠ same condition
DSTYK p.Gly493Ter Likely pathogenic ★ same condition
DSTYK c.1819-18T>A Uncertain significance ★ same condition

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/dstyk-p-arg790cys (accessed [today's date]).

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