Is DOCK6 p.Arg151Leu (c.452G>T) pathogenic?

DOCK6 p.Arg151Leu (c.452G>T) is classified Uncertain significance in DOCK6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-13). AlphaMissense: likely benign (0.1734); Ultra-rare (popmax 0.0276%, eas); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Arg151Leu (c.452G>T)?

DOCK6 p.Arg151Leu (c.452G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Arg151Leu (c.452G>T) in the general population?

DOCK6 p.Arg151Leu (c.452G>T) is ultra-rare (popmax 0.0276%, eas) (gnomAD).

What do computational predictors say about DOCK6 p.Arg151Leu (c.452G>T)?

AlphaMissense predicts likely benign (score 0.1734) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg151Leu

c.452G>T · rs374746195 · VCV2191426

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1734 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0276%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1734	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -5.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.29	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 1.4	GERP -2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0276% East Asian · 12/43,444 alleles

Filtering AF 0.0159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0125%

Overall 0.00101% 16/1,584,230 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0276%	3,620
Remaining individualsnot grpmax-eligible	0.00163%	61,464
African / African-American	0.00135%	74,314
European (non-Finnish)	0.000172%	582,761

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.Arg151Leu
Coding: c.452G>T
MANE Select: NM_020812
dbSNP: rs374746195
Type: single nucleotide variant
Location: chr19:11252174 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 151: the 'disordered' region

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.Arg151Cys Uncertain significance ★★ ⚠ same residue
DOCK6 p.Arg151His Uncertain significance ★ ⚠ same residue
DOCK6 p.Arg151Gly 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

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-arg151leu (accessed [today's date]).

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