Is DOK2 p.Arg204Pro (c.611G>C) pathogenic?

DOK2 p.Arg204Pro (c.611G>C) is classified Uncertain significance in DOK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). AlphaMissense: likely pathogenic (0.9834); Very rare (popmax 0.00891%, eas).

How common is DOK2 p.Arg204Pro (c.611G>C) in the general population?

DOK2 p.Arg204Pro (c.611G>C) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DOK2 p.Arg204Pro (c.611G>C)?

AlphaMissense predicts likely pathogenic (score 0.9834) — an in-silico prediction, not a clinical call.

DOK2 p.Arg204Pro

c.611G>C · rs756933437 · VCV2606229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9834	likely pathogenic · top 2% in DOK2
REVEL	0.79	moderately pathogenic-leaning
SaProt	LLR -14.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 0.63
Regional constraint	o/e 1.22	unconstrained · MANE · 4,287 bp · p 1.6e-07 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00891% East Asian · 4/44,882 alleles

Filtering AF 0.00733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00684%

Overall 0.00675% 109/1,613,832 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
European (non-Finnish)	0.00873%	11,457
Remaining individualsnot grpmax-eligible	0.0032%	31,238

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: DOK2
Protein: p.Arg204Pro
Coding: c.611G>C
MANE Select: NM_003974
dbSNP: rs756933437
Type: single nucleotide variant
Location: chr8:21910680 (GRCh38)
Gene constraint: LOEUF 1.838 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 2 PDB
Residue 204: the irs-type ptb domain; a β-strand

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

Similar variants

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
DOK2 p.Ala37Ser 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-arg204pro (accessed [today's date]).

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