Is DOCK6 p.Arg430His (c.1289G>A) pathogenic?

DOCK6 p.Arg430His (c.1289G>A) is classified Likely benign in DOCK6 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.1565); Low-frequency (popmax 2.05%, mid); Associated with Adams-Oliver syndrome 2.

What condition is associated with DOCK6 p.Arg430His (c.1289G>A)?

DOCK6 p.Arg430His (c.1289G>A) is associated with Adams-Oliver syndrome 2 (ClinVar).

How common is DOCK6 p.Arg430His (c.1289G>A) in the general population?

DOCK6 p.Arg430His (c.1289G>A) is low-frequency (popmax 2.05%, mid) (gnomAD).

What do computational predictors say about DOCK6 p.Arg430His (c.1289G>A)?

AlphaMissense predicts likely benign (score 0.1565) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg430His

c.1289G>A · rs143655255 · VCV771212

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1565 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.05%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Adams-Oliver syndrome 2

Computational evidence

Protein change
AlphaMissense	0.1565	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -7.88	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 7.4	GERP 2, 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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.05% Middle Eastern · 124/6,046 alleles

Filtering AF 1.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.65%

Overall 0.305% 4,882/1,600,392 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.05%	49
Admixed American	0.829%	121
Remaining individualsnot grpmax-eligible	0.465%	215
Ashkenazi Jewishnot grpmax-eligible	0.41%	244
European (non-Finnish)	0.303%	330
South Asian	0.271%	369
African / African-American	0.0936%	1,069
Finnishnot grpmax-eligible	0.0048%	20,834
East Asian	0.00452%	22,107

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.Arg430His
Coding: c.1289G>A
MANE Select: NM_020812
dbSNP: rs143655255
Type: single nucleotide variant
Location: chr19:11243355 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 430: the 'disordered' region

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

Disease context

Adams-Oliver syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK6 c.5939+2T>C Pathogenic ★★ same condition
DOCK6 c.807-1G>A Likely pathogenic ★★ same condition
DOCK6 p.Arg1526Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Arg184Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Arg488Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Gln1188Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Tyr129Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Tyr235Ter Pathogenic/Likely pathogenic ★★ 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-arg430his (accessed [today's date]).

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