Is DSTYK p.Pro16Ala (c.46C>G) pathogenic?

DSTYK p.Pro16Ala (c.46C>G) is classified Uncertain significance in DSTYK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: likely benign (0.0666); Very rare (popmax 0.00926%, eas).

How common is DSTYK p.Pro16Ala (c.46C>G) in the general population?

DSTYK p.Pro16Ala (c.46C>G) is very rare (popmax 0.00926%, eas) (gnomAD).

What do computational predictors say about DSTYK p.Pro16Ala (c.46C>G)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

DSTYK p.Pro16Ala

c.46C>G · VCV3273941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00926%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -5.85	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 9.2	GERP 1.5, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 240 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	23.4	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 0.00926% East Asian · 4/43,216 alleles

Filtering AF 0.00316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00185%

Overall 0.000443% 7/1,580,496 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00926%	10,804
South Asian	0.00341%	29,325

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.Pro16Ala
Coding: c.46C>G
MANE Select: NM_015375
Type: single nucleotide variant
Location: chr1:205211490 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 16: 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.Pro16Ser 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
DSTYK p.Arg626Gln 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-pro16ala (accessed [today's date]).

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