Is DSTYK p.Glu190Ala (c.569A>C) pathogenic?

DSTYK p.Glu190Ala (c.569A>C) is classified Uncertain significance in DSTYK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-10). AlphaMissense: likely benign (0.1126); Rare (popmax 0.113%, nfe).

How common is DSTYK p.Glu190Ala (c.569A>C) in the general population?

DSTYK p.Glu190Ala (c.569A>C) is rare (popmax 0.113%, nfe) (gnomAD).

What do computational predictors say about DSTYK p.Glu190Ala (c.569A>C)?

AlphaMissense predicts likely benign (score 0.1126) — an in-silico prediction, not a clinical call.

DSTYK p.Glu190Ala

c.569A>C · rs199548630 · VCV2069375

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1126 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.113%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1126	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 54 kb · p 2.6e-11 · regional, not allelic
Overall
CADD	20.8	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 0.113% European (non-Finnish) · 1,328/1,180,036 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.0843% 1,360/1,614,088 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.113%	889
Remaining individualsnot grpmax-eligible	0.0304%	3,289
African / African-American	0.012%	8,326
Admixed American	0.00333%	30,002
Finnishnot grpmax-eligible	0.00156%	64,036
South Asian	0.0011%	91,086

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.Glu190Ala
Coding: c.569A>C
MANE Select: NM_015375
dbSNP: rs199548630
Type: single nucleotide variant
Location: chr1:205187503 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 190: a UniProt-annotated variant site (in cakut1; uncertain significance)

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

Similar variants

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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
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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-glu190ala (accessed [today's date]).

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