Is DOCK6 p.Thr455fs (c.1362_1365del) pathogenic?

DOCK6 p.Thr455fs (c.13621365del) is classified Pathogenic/Likely pathogenic in DOCK6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-29). Ultra-rare (popmax 0.0214%, afr); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Thr455fs (c.1362_1365del)?

DOCK6 p.Thr455fs (c.1362_1365del) is associated with Inborn genetic diseases, Adams-Oliver syndrome, Adams-Oliver syndrome 2 (ClinVar).

How common is DOCK6 p.Thr455fs (c.1362_1365del) in the general population?

DOCK6 p.Thr455fs (c.1362_1365del) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

DOCK6 p.Thr455fs

c.1362_1365del · rs730882238 · VCV183335

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Conditions

Inborn genetic diseases

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 12 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Overall
CADD	34.0	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 0.0214% African / African-American · 16/74,862 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00485% 78/1,609,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0214%	4,679
East Asian	0.0067%	14,921
European (non-Finnish)	0.0045%	22,230
South Asian	0.00332%	30,110
Remaining individualsnot grpmax-eligible	0.00321%	31,129
Admixed American	0.00169%	59,152

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.Thr455fs
Coding: c.1362_1365del
MANE Select: NM_020812
dbSNP: rs730882238
Type: Deletion
Location: chr19:11243279 (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

Also linked: Adams-Oliver syndrome Adams-Oliver syndrome 2

Similar variants

DOCK6 p.Cys1061fs Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Leu1064fs Pathogenic ★★ same condition
DOCK6 p.Ser1249fs Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Asp1316_Met1317insTer Pathogenic ★ same condition
DOCK6 p.Asp427fs Pathogenic ★ same condition
DOCK6 p.Gln434fs Pathogenic ★ same condition
DOCK6 p.Glu1609fs Pathogenic ★ same condition
DOCK6 p.Glu1688fs Likely pathogenic ★ 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-thr455fs (accessed [today's date]).

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