Is DSTYK p.Ser144Thr (c.431G>C) pathogenic?

DSTYK p.Ser144Thr (c.431G>C) is classified Uncertain significance in DSTYK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-07). AlphaMissense: likely benign (0.0745); Absent from gnomAD v4.1.

How common is DSTYK p.Ser144Thr (c.431G>C) in the general population?

DSTYK p.Ser144Thr (c.431G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSTYK p.Ser144Thr (c.431G>C)?

AlphaMissense predicts likely benign (score 0.0745) — an in-silico prediction, not a clinical call.

DSTYK p.Ser144Thr

c.431G>C · rs759554676 · VCV2127117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0745 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0745	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -6.74	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 0.18	GERP -3.1, phastCons 0.002
Regional constraint	o/e 0.77	unconstrained · MANE · 54 kb · p 2.6e-11 · regional, not allelic
Overall
CADD	9.248	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.Ser144Thr
Coding: c.431G>C
MANE Select: NM_015375
dbSNP: rs759554676
Type: single nucleotide variant
Location: chr1:205187641 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 144: 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-ser144thr (accessed [today's date]).

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