Is DOCK6 p.Arg573Ter (c.1717C>T) pathogenic?

DOCK6 p.Arg573Ter (c.1717C>T) is classified Likely pathogenic in DOCK6 (ClinVar, Single submitter, 2 submitters; last evaluated 2020-02-07). Very rare (popmax 0.0011%, nfe); Associated with DOCK6-related disorders.

What condition is associated with DOCK6 p.Arg573Ter (c.1717C>T)?

DOCK6 p.Arg573Ter (c.1717C>T) is associated with DOCK6-related disorders (ClinVar).

How common is DOCK6 p.Arg573Ter (c.1717C>T) in the general population?

DOCK6 p.Arg573Ter (c.1717C>T) is very rare (popmax 0.0011%, nfe) (gnomAD).

DOCK6 p.Arg573Ter

c.1717C>T · VCV4434023

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

DOCK6-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 48
Splicing
SpliceAI	Δ0.88	donor gain · deltas
Pangolin	Δ0.46	gain · loss 0.26 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.81	GERP -5, phastCons 0.01
Overall
CADD	52.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,564 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00093% 15/1,613,400 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,444
European (non-Finnish)grpmax	0.0011%	90,736
South Asian	0.0011%	91,084

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg573Ter
Coding: c.1717C>T
MANE Select: NM_020812
Type: single nucleotide variant
Location: chr19:11238231 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 573: the c2 dock-type domain

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

Disease context

DOCK6-related disorders

Similar variants

DOCK6 p.Arg573Gln Uncertain significance ★★ ⚠ 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.Arg1332Pro Uncertain significance ★ ⚠ 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-arg573ter (accessed [today's date]).

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