Is DOK2 p.Arg130Trp (c.388C>T) pathogenic?

DOK2 p.Arg130Trp (c.388C>T) is classified Uncertain significance in DOK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-27). AlphaMissense: likely benign (0.0689); Ultra-rare (popmax 0.023%, amr).

How common is DOK2 p.Arg130Trp (c.388C>T) in the general population?

DOK2 p.Arg130Trp (c.388C>T) is ultra-rare (popmax 0.023%, amr) (gnomAD).

What do computational predictors say about DOK2 p.Arg130Trp (c.388C>T)?

AlphaMissense predicts likely benign (score 0.0689) — an in-silico prediction, not a clinical call.

DOK2 p.Arg130Trp

c.388C>T · rs777211002 · VCV2568525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0689 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0689	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -8.31	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 0.021	GERP -3.2
Regional constraint	o/e 1.22	unconstrained · MANE · 4,287 bp · p 1.6e-07 · regional, not allelic
Overall
CADD	14.23	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 0.023% Admixed American · 12/52,146 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0103%

Overall 0.00314% 49/1,562,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.023%	4,346
African / African-American	0.0135%	7,381
Remaining individualsnot grpmax-eligible	0.0066%	15,142
South Asian	0.00353%	28,332
European (non-Finnish)	0.00173%	57,656

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.Arg130Trp
Coding: c.388C>T
MANE Select: NM_003974
dbSNP: rs777211002
Type: single nucleotide variant
Location: chr8:21911946 (GRCh38)
Gene constraint: LOEUF 1.838 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 2 PDB

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-arg130trp (accessed [today's date]).

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