Is DSTYK p.Arg29Gln (c.86G>A) pathogenic?

DSTYK p.Arg29Gln (c.86G>A) is classified Conflicting classifications of pathogenicity in DSTYK (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-11-04). AlphaMissense: likely benign (0.2087); Rare (popmax 0.166%, mid); Associated with congenital anomalies of kidney and urinary tract 1.

What condition is associated with DSTYK p.Arg29Gln (c.86G>A)?

DSTYK p.Arg29Gln (c.86G>A) is associated with congenital anomalies of kidney and urinary tract 1 (ClinVar).

How common is DSTYK p.Arg29Gln (c.86G>A) in the general population?

DSTYK p.Arg29Gln (c.86G>A) is rare (popmax 0.166%, mid) (gnomAD).

What do computational predictors say about DSTYK p.Arg29Gln (c.86G>A)?

AlphaMissense predicts likely benign (score 0.2087) — an in-silico prediction, not a clinical call.

DSTYK p.Arg29Gln

c.86G>A · rs200780796 · VCV60687

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.2087 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.166%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital anomalies of kidney and urinary tract 1

Computational evidence

Protein change
AlphaMissense	0.2087	likely benign
REVEL	0.384	indeterminate
SaProt	LLR -6.26	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 7.2	GERP 2.4, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 240 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	25.6	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 0.166% Middle Eastern · 10/6,012 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.0658% 1,052/1,599,294 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.897%	111
Middle Easterngrpmax	0.166%	601
South Asian	0.165%	607
Admixed American	0.113%	884
Remaining individualsnot grpmax-eligible	0.0919%	1,088
European (non-Finnish)	0.0424%	2,357
African / African-American	0.0107%	9,330

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg29Gln
Coding: c.86G>A
MANE Select: NM_015375
dbSNP: rs200780796
Type: single nucleotide variant
Location: chr1:205211450 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 29: 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.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
DSTYK c.1819-3C>T Conflicting classifications of pathogenicity ★ 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-arg29gln (accessed [today's date]).

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