Is DOK3 p.Arg3Trp (c.7C>T) pathogenic?

DOK3 p.Arg3Trp (c.7C>T) is classified Uncertain significance in DOK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.1967); Very rare (popmax 0.00667%, afr).

How common is DOK3 p.Arg3Trp (c.7C>T) in the general population?

DOK3 p.Arg3Trp (c.7C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about DOK3 p.Arg3Trp (c.7C>T)?

AlphaMissense predicts likely benign (score 0.1967) — an in-silico prediction, not a clinical call.

DOK3 p.Arg3Trp

c.7C>T · rs558150906 · VCV3085184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1967 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1967	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -7.48	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 0.45	GERP 0.001, phastCons 0.31
Overall
CADD	9.954	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 0.00667% African / African-American · 5/74,944 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000869% 14/1,610,762 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,989
South Asian	0.0022%	45,481
Remaining individualsnot grpmax-eligible	0.0016%	62,310
European (non-Finnish)	0.000509%	196,643

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: DOK3
Protein: p.Arg3Trp
Coding: c.7C>T
MANE Select: NM_001308236 · reported on NM_024872
dbSNP: rs558150906
Type: single nucleotide variant
Location: chr5:177509846 (GRCh38)
Gene constraint: LOEUF 1.47 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.94

Full DOK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK3 p.Arg3Pro Uncertain significance ★ ⚠ same residue
DOK3 p.Arg3Gln Likely benign ★ same residue
DOK3 c.-102G>T Uncertain significance ★ ⚠ same type
DOK3 c.-181C>T Uncertain significance ★ ⚠ same type
DOK3 c.-182G>A Uncertain significance ★ ⚠ same type
DOK3 c.-182G>C Uncertain significance ★ ⚠ same type
DOK3 c.-23C>T Uncertain significance ★ ⚠ same type
DOK3 c.-35G>A 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/dok3-p-arg3trp (accessed [today's date]).

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