Is DOCK6 p.Arg1340His (c.4019G>A) pathogenic?

DOCK6 p.Arg1340His (c.4019G>A) is classified Uncertain significance in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: likely pathogenic (0.6977); Very rare (popmax 0.0028%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Arg1340His (c.4019G>A)?

DOCK6 p.Arg1340His (c.4019G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Arg1340His (c.4019G>A) in the general population?

DOCK6 p.Arg1340His (c.4019G>A) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about DOCK6 p.Arg1340His (c.4019G>A)?

AlphaMissense predicts likely pathogenic (score 0.6977) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg1340His

c.4019G>A · VCV3504512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6977 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6977	likely pathogenic
REVEL	0.202	benign-leaning
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	31.0	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 0.0028% European (non-Finnish) · 33/1,179,876 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00223% 36/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,754
African / African-American	0.00266%	37,535
South Asian	0.0011%	91,080

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.Arg1340His
Coding: c.4019G>A
MANE Select: NM_020812
Type: single nucleotide variant
Location: chr19:11215803 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK6 p.Arg1340Cys Conflicting classifications of pathogenicity ★ ⚠ 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
DOCK6 p.Ala133Thr 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-arg1340his (accessed [today's date]).

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