Is DOCK6 p.Ala211fs (c.631del) pathogenic?

DOCK6 p.Ala211fs (c.631del) is classified Pathogenic/Likely pathogenic in DOCK6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-23). Very rare (popmax 0.00458%, nfe); Associated with DOCK6-related disorders.

What condition is associated with DOCK6 p.Ala211fs (c.631del)?

DOCK6 p.Ala211fs (c.631del) is associated with DOCK6-related disorders, intellectual disability (ClinVar).

How common is DOCK6 p.Ala211fs (c.631del) in the general population?

DOCK6 p.Ala211fs (c.631del) is very rare (popmax 0.00458%, nfe) (gnomAD).

DOCK6 p.Ala211fs

c.631del · rs761856660 · VCV975216

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Conditions

DOCK6-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.5	GERP 0.13, phastCons 1
Overall
CADD	25.2	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 0.00458% European (non-Finnish) · 54/1,179,842 alleles

Filtering AF 0.00358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00353% 57/1,613,652 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,817
European (non-Finnish)grpmax	0.00458%	21,849

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.Ala211fs
Coding: c.631del
MANE Select: NM_020812
dbSNP: rs761856660
Type: Deletion
Location: chr19:11250963 (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

DOCK6-related disorders

Also linked: intellectual disability

Similar variants

DOCK6 p.Ser1249fs Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Ala211= Likely benign ★★ same residue
DOCK6 p.His609fs Likely pathogenic ★ same condition
DOCK6 p.Pro1066fs Pathogenic ★ same condition
DOCK6 c.1644-5del Likely benign same condition
DOCK6 p.Arg488Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Arg174Cys Uncertain significance ★★ ⚠ same condition
DOCK6 p.Arg1971Gln 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-ala211fs (accessed [today's date]).

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