Is DSTYK p.Arg35Cys (c.103C>T) pathogenic?

DSTYK p.Arg35Cys (c.103C>T) is classified Uncertain significance in DSTYK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). AlphaMissense: likely benign (0.1616); Very rare (popmax 0.00134%, afr).

How common is DSTYK p.Arg35Cys (c.103C>T) in the general population?

DSTYK p.Arg35Cys (c.103C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DSTYK p.Arg35Cys (c.103C>T)?

AlphaMissense predicts likely benign (score 0.1616) — an in-silico prediction, not a clinical call.

DSTYK p.Arg35Cys

c.103C>T · rs1431767340 · VCV2639849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1616 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1616	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -9.43	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 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 240 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	27.2	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

Grpmax group 0.00134% African / African-American · 1/74,866 alleles

Overall 6.88e-05% 1/1,453,362 alleles · very rare

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.Arg35Cys
Coding: c.103C>T
MANE Select: NM_015375
dbSNP: rs1431767340
Type: single nucleotide variant
Location: chr1:205211433 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 35: a UniProt-annotated variant site (in cakut1; uncertain significance)

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

Similar variants

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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-arg35cys (accessed [today's date]).

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