Is DSTYK p.Glu439Asp (c.1317G>C) pathogenic?

DSTYK p.Glu439Asp (c.1317G>C) is classified Uncertain significance in DSTYK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: likely benign (0.0994); Absent from gnomAD v4.1; Associated with congenital anomalies of kidney and urinary tract 1.

How common is DSTYK p.Glu439Asp (c.1317G>C) in the general population?

DSTYK p.Glu439Asp (c.1317G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSTYK p.Glu439Asp (c.1317G>C)?

AlphaMissense predicts likely benign (score 0.0994) — an in-silico prediction, not a clinical call.

DSTYK p.Glu439Asp

Q: What condition is associated with DSTYK p.Glu439Asp (c.1317G>C)?

DSTYK p.Glu439Asp (c.1317G>C) is associated with congenital anomalies of kidney and urinary tract 1, hereditary spastic paraplegia 23 (ClinVar).

c.1317G>C · VCV3578158

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital anomalies of kidney and urinary tract 1

Computational evidence

Protein change
AlphaMissense	0.0994	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -8.02	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 -0.21	GERP -3.1, phastCons 0.27
Regional constraint	o/e 0.77	unconstrained · MANE · 54 kb · p 2.6e-11 · regional, not allelic
Overall
CADD	13.17	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSTYK
Protein: p.Glu439Asp
Coding: c.1317G>C
MANE Select: NM_015375
Type: single nucleotide variant
Location: chr1:205169170 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 439: a UniProt-annotated variant site (in cakut1; uncertain significance)

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

Disease context

congenital anomalies of kidney and urinary tract 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 23

Similar variants

DSTYK p.Arg626Gln Uncertain significance ★★ ⚠ same condition
DSTYK p.Gly32Asp Uncertain significance ★★ ⚠ same condition
DSTYK p.His203Gln Uncertain significance ★★ ⚠ same condition
DSTYK p.Cys641Arg Benign ★★ same condition
DSTYK p.Phe676= Benign ★★ same condition
DSTYK p.Gln465Arg Likely pathogenic ★ ⚠ same condition
DSTYK p.Gly493Ter Likely pathogenic ★ same condition
DSTYK c.1819-18T>A Uncertain significance ★ same condition

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-glu439asp (accessed [today's date]).

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