Is DOK2 p.Pro290Thr (c.868C>A) pathogenic?

DOK2 p.Pro290Thr (c.868C>A) is classified Uncertain significance in DOK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). AlphaMissense: likely benign (0.0632); Absent from gnomAD v4.1.

How common is DOK2 p.Pro290Thr (c.868C>A) in the general population?

DOK2 p.Pro290Thr (c.868C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOK2 p.Pro290Thr (c.868C>A)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

DOK2 p.Pro290Thr

c.868C>A · rs1809750943 · VCV2284998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -8.75	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 -0.82	GERP -3.5
Regional constraint	o/e 1.22	unconstrained · MANE · 4,287 bp · p 1.6e-07 · regional, not allelic
Overall
CADD	1.28	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: DOK2
Protein: p.Pro290Thr
Coding: c.868C>A
MANE Select: NM_003974
dbSNP: rs1809750943
Type: single nucleotide variant
Location: chr8:21909682 (GRCh38)
Gene constraint: LOEUF 1.838 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 2 PDB
Residue 290: the 'disordered' region

Full DOK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK2 p.Pro290Ser Uncertain significance ★ ⚠ same residue
DOK2 p.Ser394Ala Benign ★★ same type
DOK2 p.Ala113Thr Uncertain significance ★ ⚠ same type
DOK2 p.Ala160Thr Uncertain significance ★ ⚠ same type
DOK2 p.Ala237Val Uncertain significance ★ ⚠ same type
DOK2 p.Ala28Pro Uncertain significance ★ ⚠ same type
DOK2 p.Ala372Val Uncertain significance ★ ⚠ same type
DOK2 p.Ala379Val 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/dok2-p-pro290thr (accessed [today's date]).

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