Is DOCK6 p.Arg1971Trp (c.5911C>T) pathogenic?

DOCK6 p.Arg1971Trp (c.5911C>T) is classified Uncertain significance in DOCK6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-19). AlphaMissense: likely pathogenic (0.9391); Ultra-rare (popmax 0.0217%, amr); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Arg1971Trp (c.5911C>T)?

DOCK6 p.Arg1971Trp (c.5911C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Arg1971Trp (c.5911C>T) in the general population?

DOCK6 p.Arg1971Trp (c.5911C>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about DOCK6 p.Arg1971Trp (c.5911C>T)?

AlphaMissense predicts likely pathogenic (score 0.9391) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg1971Trp

c.5911C>T · rs376594140 · VCV2068104

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9391 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9391	likely pathogenic
REVEL	0.389	indeterminate
SaProt	LLR -16.89	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 2.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	25.7	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 0.0217% Admixed American · 13/59,962 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00217% 35/1,613,320 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,612
South Asian	0.0022%	45,502
European (non-Finnish)	0.0017%	58,982

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.Arg1971Trp
Coding: c.5911C>T
MANE Select: NM_020812
dbSNP: rs376594140
Type: single nucleotide variant
Location: chr19:11200744 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 1971: 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.Arg1971Leu Uncertain significance ★★ ⚠ same residue
DOCK6 p.Arg1971Gln 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-arg1971trp (accessed [today's date]).

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