Is DSTYK p.Pro188Ala (c.562C>G) pathogenic?

DSTYK p.Pro188Ala (c.562C>G) is classified Uncertain significance in DSTYK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-11). AlphaMissense: ambiguous (0.3806); Ultra-rare (popmax 0.0178%, eas).

How common is DSTYK p.Pro188Ala (c.562C>G) in the general population?

DSTYK p.Pro188Ala (c.562C>G) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about DSTYK p.Pro188Ala (c.562C>G)?

AlphaMissense predicts ambiguous (score 0.3806) — an in-silico prediction, not a clinical call.

DSTYK p.Pro188Ala

c.562C>G · rs199944046 · VCV2887783

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3806 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3806	ambiguous
REVEL	0.807	moderately pathogenic-leaning
SaProt	LLR -8.74	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 54 kb · p 2.6e-11 · regional, not allelic
Overall
CADD	25.1	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 0.0178% East Asian · 8/44,886 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000558% 9/1,614,154 alleles · ultra-rare exomes 8/1,461,886 · genomes 1/152,268 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,611
South Asian	0.0011%	91,082

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.Pro188Ala
Coding: c.562C>G
MANE Select: NM_015375
dbSNP: rs199944046
Type: single nucleotide variant
Location: chr1:205187510 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 188: 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.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-pro188ala (accessed [today's date]).

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