Is DSTYK p.Asp926Tyr (c.2776G>T) pathogenic?

DSTYK p.Asp926Tyr (c.2776G>T) is classified Uncertain significance in DSTYK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-08). AlphaMissense: likely benign (0.1346); Rare (popmax 0.109%, nfe); Associated with chronic kidney disease.

What condition is associated with DSTYK p.Asp926Tyr (c.2776G>T)?

DSTYK p.Asp926Tyr (c.2776G>T) is associated with chronic kidney disease (ClinVar).

How common is DSTYK p.Asp926Tyr (c.2776G>T) in the general population?

DSTYK p.Asp926Tyr (c.2776G>T) is rare (popmax 0.109%, nfe) (gnomAD).

What do computational predictors say about DSTYK p.Asp926Tyr (c.2776G>T)?

AlphaMissense predicts likely benign (score 0.1346) — an in-silico prediction, not a clinical call.

DSTYK p.Asp926Tyr

c.2776G>T · rs148542303 · VCV915849

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1346 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.109%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

chronic kidney disease

Computational evidence

Protein change
AlphaMissense	0.1346	likely benign
REVEL	0.325	indeterminate
SaProt	LLR -7.04	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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 154 bp · p 0.89 · regional, not allelic
Overall
CADD	26.4	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 0.109% European (non-Finnish) · 1,285/1,176,582 alleles

Filtering AF 0.104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.0871% 1,402/1,610,098 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.109%	916
Remaining individualsnot grpmax-eligible	0.0819%	1,221
Finnishnot grpmax-eligible	0.0687%	1,455
African / African-American	0.0187%	5,358
Admixed American	0.0133%	7,494

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.Asp926Tyr
Coding: c.2776G>T
MANE Select: NM_015375
dbSNP: rs148542303
Type: single nucleotide variant
Location: chr1:205147572 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 926: 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

chronic kidney disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DSTYK p.Asp926Asn Uncertain significance ★★ ⚠ same residue
DSTYK p.Ala206Val Uncertain significance ★★ ⚠ same type
DSTYK p.Ala477Ser Uncertain significance ★★ ⚠ same type
DSTYK p.Ala601Val Uncertain significance ★★ ⚠ same type
DSTYK p.Arg411Gln Uncertain significance ★★ ⚠ same type
DSTYK p.Arg462Gln Uncertain significance ★★ ⚠ same type
DSTYK p.Arg471Gln Uncertain significance ★★ ⚠ same type
DSTYK p.Arg626Gln 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/dstyk-p-asp926tyr (accessed [today's date]).

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