Is DSTYK p.Gly19Asp (c.56G>A) pathogenic?

DSTYK p.Gly19Asp (c.56G>A) is classified Uncertain significance in DSTYK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-17). AlphaMissense: ambiguous (0.3539); Ultra-rare (popmax 0.0311%, afr).

How common is DSTYK p.Gly19Asp (c.56G>A) in the general population?

DSTYK p.Gly19Asp (c.56G>A) is ultra-rare (popmax 0.0311%, afr) (gnomAD).

What do computational predictors say about DSTYK p.Gly19Asp (c.56G>A)?

AlphaMissense predicts ambiguous (score 0.3539) — an in-silico prediction, not a clinical call.

DSTYK p.Gly19Asp

c.56G>A · rs774633972 · VCV2623377

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3539 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0311%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3539	ambiguous
REVEL	0.219	benign-leaning
SaProt	LLR -7.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 2.4, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 240 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	23.0	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 0.0311% African / African-American · 23/73,944 alleles

Filtering AF 0.0212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00164% 26/1,584,930 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0311%	3,215
Admixed American	0.00172%	58,048
European (non-Finnish)	0.000171%	584,918

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.Gly19Asp
Coding: c.56G>A
MANE Select: NM_015375
dbSNP: rs774633972
Type: single nucleotide variant
Location: chr1:205211480 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 19: 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.Gly19Ser Uncertain significance ★ ⚠ same residue
DSTYK p.Gly19_Gly20insProGly Uncertain significance ★ 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
DSTYK p.Arg471Gln 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-gly19asp (accessed [today's date]).

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