Is DSTYK p.Arg592Gln (c.1775G>A) pathogenic?

DSTYK p.Arg592Gln (c.1775G>A) is classified Conflicting classifications of pathogenicity in DSTYK (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-03). AlphaMissense: likely pathogenic (0.7172); Rare (popmax 0.393%, afr); Associated with congenital anomalies of kidney and urinary tract 1.

What condition is associated with DSTYK p.Arg592Gln (c.1775G>A)?

DSTYK p.Arg592Gln (c.1775G>A) is associated with congenital anomalies of kidney and urinary tract 1 (ClinVar).

How common is DSTYK p.Arg592Gln (c.1775G>A) in the general population?

DSTYK p.Arg592Gln (c.1775G>A) is rare (popmax 0.393%, afr) (gnomAD).

What do computational predictors say about DSTYK p.Arg592Gln (c.1775G>A)?

AlphaMissense predicts likely pathogenic (score 0.7172) — an in-silico prediction, not a clinical call.

DSTYK p.Arg592Gln

c.1775G>A · rs148815814 · VCV224356

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7172 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.393%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital anomalies of kidney and urinary tract 1

Computational evidence

Protein change
AlphaMissense	0.7172	likely pathogenic
REVEL	0.609	indeterminate
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 54 kb · p 2.6e-11 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.393% African / African-American · 295/74,994 alleles

Filtering AF 0.356% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.342%

Overall 0.0254% 410/1,614,004 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.393%	254
East Asian	0.165%	606
Admixed American	0.0267%	3,751
Remaining individualsnot grpmax-eligible	0.016%	6,251
South Asian	0.0022%	45,535
European (non-Finnish)	0.0011%	90,767

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.Arg592Gln
Coding: c.1775G>A
MANE Select: NM_015375
dbSNP: rs148815814
Type: single nucleotide variant
Location: chr1:205162079 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 592: 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.Arg592Trp 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-arg592gln (accessed [today's date]).

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