Is DSTYK p.Pro98Ala (c.292C>G) pathogenic?

DSTYK p.Pro98Ala (c.292C>G) is classified Uncertain significance in DSTYK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-09). AlphaMissense: likely benign (0.0588); Ultra-rare (popmax 0.0267%, eas).

How common is DSTYK p.Pro98Ala (c.292C>G) in the general population?

DSTYK p.Pro98Ala (c.292C>G) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about DSTYK p.Pro98Ala (c.292C>G)?

AlphaMissense predicts likely benign (score 0.0588) — an in-silico prediction, not a clinical call.

DSTYK p.Pro98Ala

c.292C>G · VCV4695968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0588 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0588	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.80	acceptor gain · deltas
Pangolin	Δ0.65	gain · loss 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.5	GERP 0.33, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 54 kb · p 2.6e-11 · regional, not allelic
Overall
CADD	23.7	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 0.0267% East Asian · 12/44,886 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.000868% 14/1,613,428 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,740
Admixed American	0.00167%	59,928
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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.Pro98Ala
Coding: c.292C>G
MANE Select: NM_015375
Type: single nucleotide variant
Location: chr1:205187780 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 98: 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.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-pro98ala (accessed [today's date]).

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