Is DOCK6 p.Arg1872Cys (c.5614C>T) pathogenic?

DOCK6 p.Arg1872Cys (c.5614C>T) is classified Uncertain significance in DOCK6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-05). AlphaMissense: likely pathogenic (0.6645); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Arg1872Cys (c.5614C>T)?

DOCK6 p.Arg1872Cys (c.5614C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Arg1872Cys (c.5614C>T) in the general population?

DOCK6 p.Arg1872Cys (c.5614C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about DOCK6 p.Arg1872Cys (c.5614C>T)?

AlphaMissense predicts likely pathogenic (score 0.6645) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg1872Cys

c.5614C>T · rs189395618 · VCV1516139

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6645 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6645	likely pathogenic
REVEL	0.674	pathogenic-leaning
SaProt	LLR -14.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.5	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	34.0	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 0.00334% Admixed American · 2/59,904 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.0018% 29/1,613,460 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,952
European (non-Finnish)	0.0022%	45,371
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Arg1872Cys
Coding: c.5614C>T
MANE Select: NM_020812
dbSNP: rs189395618
Type: single nucleotide variant
Location: chr19:11201963 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 1872: 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 p.Arg1872His Uncertain significance ★ ⚠ same residue
DOCK6 p.Arg1872Pro Uncertain significance ★ ⚠ same residue
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

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-arg1872cys (accessed [today's date]).

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