Is DSTYK p.Trp8Leu (c.23G>T) pathogenic?

DSTYK p.Trp8Leu (c.23G>T) is classified Uncertain significance in DSTYK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-11). AlphaMissense: likely benign (0.0897); Absent from gnomAD v4.1.

How common is DSTYK p.Trp8Leu (c.23G>T) in the general population?

DSTYK p.Trp8Leu (c.23G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSTYK p.Trp8Leu (c.23G>T)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

DSTYK p.Trp8Leu

c.23G>T · VCV4929940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,560,082)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -4.26	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 2.4	GERP 0.53, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 240 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	21.2	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

No allele count reported in gnomAD v4.1 (AN 1,560,082). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DSTYK
Protein: p.Trp8Leu
Coding: c.23G>T
MANE Select: NM_015375
Type: single nucleotide variant
Location: chr1:205211513 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 8: a UniProt-annotated variant site (in cakut1; uncertain significance); the 'disordered' region

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

Similar variants

DSTYK p.Trp8Gly Uncertain significance ★★ ⚠ same residue
DSTYK p.Trp8Arg Uncertain significance ★ ⚠ same residue
DSTYK p.Trp8Ter Pathogenic 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

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-trp8leu (accessed [today's date]).

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