Is DOCK6 p.Ser1511fs (c.4531_4532del) pathogenic?

DOCK6 p.Ser1511fs (c.45314532del) is classified Likely pathogenic in DOCK6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-04). Very rare (popmax 0.00267%, afr); Associated with Adams-Oliver syndrome 2.

What condition is associated with DOCK6 p.Ser1511fs (c.4531_4532del)?

DOCK6 p.Ser1511fs (c.4531_4532del) is associated with Adams-Oliver syndrome 2, Adams-Oliver syndrome (ClinVar).

How common is DOCK6 p.Ser1511fs (c.4531_4532del) in the general population?

DOCK6 p.Ser1511fs (c.4531_4532del) is very rare (popmax 0.00267%, afr) (gnomAD).

DOCK6 p.Ser1511fs

c.4531_4532del · VCV3779280

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Adams-Oliver syndrome 2

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 36 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -20	GERP -5
Overall
CADD	35.0	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 0.00267% African / African-American · 2/74,820 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00112% 18/1,611,918 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,410
European (non-Finnish)	0.00127%	78,645
South Asian	0.0011%	90,920

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.Ser1511fs
Coding: c.4531_4532del
MANE Select: NM_020812
Type: Microsatellite
Location: chr19:11212111 (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

Adams-Oliver syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Adams-Oliver syndrome

Similar variants

DOCK6 p.Leu207fs Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Lys1928fs Pathogenic ★★ same condition
DOCK6 p.Ser1511= Likely benign ★ same residue
DOCK6 c.5939+2T>C Pathogenic ★★ same condition
DOCK6 c.807-1G>A Likely pathogenic ★★ same condition
DOCK6 p.Arg1526Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Arg184Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Arg488Ter Pathogenic/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-ser1511fs (accessed [today's date]).

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