Is DSTYK p.Pro16Ser (c.46C>T) pathogenic?

DSTYK p.Pro16Ser (c.46C>T) is classified Uncertain significance in DSTYK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-29). AlphaMissense: likely benign (0.0886); Ultra-rare (popmax 0.017%, mid).

How common is DSTYK p.Pro16Ser (c.46C>T) in the general population?

DSTYK p.Pro16Ser (c.46C>T) is ultra-rare (popmax 0.017%, mid) (gnomAD).

What do computational predictors say about DSTYK p.Pro16Ser (c.46C>T)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

DSTYK p.Pro16Ser

c.46C>T · rs761213465 · VCV1905588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -6.33	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	24.0	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 0.017% Middle Eastern · 1/5,896 alleles

Filtering AF 0.0081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00598%

Overall 0.00146% 23/1,580,496 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,896
Admixed American	0.0156%	6,420
Remaining individualsnot grpmax-eligible	0.0049%	20,411
East Asian	0.00231%	43,216
African / African-American	0.00136%	73,478
European (non-Finnish)	0.000685%	146,005

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.Pro16Ser
Coding: c.46C>T
MANE Select: NM_015375
dbSNP: rs761213465
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.Pro16Ala 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-pro16ser (accessed [today's date]).

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