Is DSTYK p.Val6Ala (c.17T>C) pathogenic?

DSTYK p.Val6Ala (c.17T>C) is classified Uncertain significance in DSTYK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-27). AlphaMissense: likely benign (0.0762); Ultra-rare (popmax 0.0217%, amr).

How common is DSTYK p.Val6Ala (c.17T>C) in the general population?

DSTYK p.Val6Ala (c.17T>C) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about DSTYK p.Val6Ala (c.17T>C)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

DSTYK p.Val6Ala

c.17T>C · VCV3707082

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -5.42	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 2.5	GERP -2.5, phastCons 0.004
Regional constraint	o/e 1.40	unconstrained · MANE · 240 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	9.019	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 0.0217% Admixed American · 12/55,252 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0098%

Overall 0.00122% 19/1,551,764 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,604
Remaining individualsnot grpmax-eligible	0.00333%	30,050
European (non-Finnish)	0.000433%	231,132

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.Val6Ala
Coding: c.17T>C
MANE Select: NM_015375
Type: single nucleotide variant
Location: chr1:205211519 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 6: the 'disordered' region

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

Similar variants

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
DSTYK p.Arg635His 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-val6ala (accessed [today's date]).

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