Is DOCK6 p.Arg1332Pro (c.3995G>C) pathogenic?

DOCK6 p.Arg1332Pro (c.3995G>C) is classified Uncertain significance in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). AlphaMissense: likely pathogenic (0.9929); Very rare (popmax 8.48e-05%, nfe); Associated with DOCK6-related disorder.

What condition is associated with DOCK6 p.Arg1332Pro (c.3995G>C)?

DOCK6 p.Arg1332Pro (c.3995G>C) is associated with DOCK6-related disorder (ClinVar).

How common is DOCK6 p.Arg1332Pro (c.3995G>C) in the general population?

DOCK6 p.Arg1332Pro (c.3995G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DOCK6 p.Arg1332Pro (c.3995G>C)?

AlphaMissense predicts likely pathogenic (score 0.9929) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg1332Pro

c.3995G>C · rs764432170 · VCV2635901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9929 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DOCK6-related disorder

Computational evidence

Protein change
AlphaMissense	0.9929	likely pathogenic · top 3% in DOCK6
REVEL	0.46	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	24.2	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 8.48e-05% European (non-Finnish) · 1/1,179,878 alleles

Overall 6.84e-05% 1/1,461,666 alleles · very rare

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.Arg1332Pro
Coding: c.3995G>C
MANE Select: NM_020812
dbSNP: rs764432170
Type: single nucleotide variant
Location: chr19:11215827 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB

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

Disease context

DOCK6-related disorder

Similar variants

DOCK6 p.Arg1332Ter Pathogenic ★ same residue
DOCK6 p.Arg488Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Arg174Cys Uncertain significance ★★ ⚠ same condition
DOCK6 p.Arg1971Gln Uncertain significance ★★ ⚠ same condition
DOCK6 p.Gly827Val Uncertain significance ★★ ⚠ same condition
DOCK6 c.3711+1G>C Likely pathogenic ★ same condition
DOCK6 p.Arg573Ter Likely pathogenic ★ same condition
DOCK6 p.Arg1843Cys 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-arg1332pro (accessed [today's date]).

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