Is DSTYK p.Lys328Thr (c.983A>C) pathogenic?

DSTYK p.Lys328Thr (c.983A>C) is classified Likely benign in DSTYK (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-25). AlphaMissense: likely benign (0.1139); Rare (popmax 0.549%, afr).

How common is DSTYK p.Lys328Thr (c.983A>C) in the general population?

DSTYK p.Lys328Thr (c.983A>C) is rare (popmax 0.549%, afr) (gnomAD).

What do computational predictors say about DSTYK p.Lys328Thr (c.983A>C)?

AlphaMissense predicts likely benign (score 0.1139) — an in-silico prediction, not a clinical call.

DSTYK p.Lys328Thr

c.983A>C · rs145485055 · VCV1573434

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1139 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.549%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1139	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -3.94	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 0.29	GERP -0.15, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 54 kb · p 2.6e-11 · regional, not allelic
Overall
CADD	8.372	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 0.549% African / African-American · 412/75,008 alleles

Filtering AF 0.505% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.488%

Overall 0.0291% 469/1,614,106 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.549%	182
Remaining individualsnot grpmax-eligible	0.0528%	1,894
Admixed American	0.0217%	4,616
Middle Eastern	0.0165%	6,062
South Asian	0.00659%	15,180
European (non-Finnish)	0.000339%	295,009

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.Lys328Thr
Coding: c.983A>C
MANE Select: NM_015375
dbSNP: rs145485055
Type: single nucleotide variant
Location: chr1:205169504 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 328: 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

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
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-lys328thr (accessed [today's date]).

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