Is DOCK6 p.Arg1785Gly (c.5353C>G) pathogenic?

DOCK6 p.Arg1785Gly (c.5353C>G) is classified Uncertain significance in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). AlphaMissense: likely pathogenic (0.9827); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Arg1785Gly (c.5353C>G)?

DOCK6 p.Arg1785Gly (c.5353C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Arg1785Gly (c.5353C>G) in the general population?

DOCK6 p.Arg1785Gly (c.5353C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DOCK6 p.Arg1785Gly (c.5353C>G)?

AlphaMissense predicts likely pathogenic (score 0.9827) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg1785Gly

c.5353C>G · VCV4014237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9827	likely pathogenic · top 6% in DOCK6
REVEL	0.347	indeterminate
SaProt	LLR -12.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -2.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	27.7	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 0.00223% East Asian · 1/44,880 alleles

Overall 0.000137% 2/1,461,678 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
South Asian	0.0011%	91,080

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: DOCK6
Protein: p.Arg1785Gly
Coding: c.5353C>G
MANE Select: NM_020812
Type: single nucleotide variant
Location: chr19:11202592 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 1785: the docker domain

Full DOCK6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK6 c.5939+2T>C Pathogenic ★★ same condition
DOCK6 p.Glu1494Ter Pathogenic ★★ same condition
DOCK6 p.Ala1153Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1207Val Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1241Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1319Val Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala133Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1481Thr Uncertain significance ★★ ⚠ same condition

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/dock6-p-arg1785gly (accessed [today's date]).

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