Is DSTYK p.Ser587Thr (c.1760G>C) pathogenic?

DSTYK p.Ser587Thr (c.1760G>C) is classified Uncertain significance in DSTYK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-07). AlphaMissense: likely benign (0.1793); Ultra-rare (popmax 0.0133%, amr); Associated with DSTYK-related disorder.

What condition is associated with DSTYK p.Ser587Thr (c.1760G>C)?

DSTYK p.Ser587Thr (c.1760G>C) is associated with DSTYK-related disorder (ClinVar).

How common is DSTYK p.Ser587Thr (c.1760G>C) in the general population?

DSTYK p.Ser587Thr (c.1760G>C) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about DSTYK p.Ser587Thr (c.1760G>C)?

AlphaMissense predicts likely benign (score 0.1793) — an in-silico prediction, not a clinical call.

DSTYK p.Ser587Thr

c.1760G>C · rs374851853 · VCV2187389

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1793 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DSTYK-related disorder

Computational evidence

Protein change
AlphaMissense	0.1793	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -7.20	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 2.3, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 54 kb · p 2.6e-11 · regional, not allelic
Overall
CADD	22.9	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 0.0133% Admixed American · 8/60,020 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00223% 36/1,614,148 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,502
Finnishnot grpmax-eligible	0.00625%	16,011
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	0.00178%	56,191

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.Ser587Thr
Coding: c.1760G>C
MANE Select: NM_015375
dbSNP: rs374851853
Type: single nucleotide variant
Location: chr1:205162094 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 587: 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

DSTYK-related disorder

Similar variants

DSTYK p.Gly744Ala Uncertain significance ★ ⚠ same condition
DSTYK p.Met212Thr Uncertain significance ★ same condition
DSTYK p.Thr538Ser Uncertain significance ★ ⚠ same condition
DSTYK p.Arg870Cys Uncertain significance ⚠ same condition
DSTYK p.Gly900= Uncertain significance same condition
DSTYK p.Ser577Arg Uncertain significance ⚠ same condition
DSTYK p.Ile55= Likely benign same condition
DSTYK p.Ala206Val 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-ser587thr (accessed [today's date]).

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