Is DOCK6 p.Tyr835= (c.2505C>T) pathogenic?

DOCK6 p.Tyr835= (c.2505C>T) is classified Likely benign in DOCK6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0929%, nfe); Associated with Adams-Oliver syndrome 2.

What condition is associated with DOCK6 p.Tyr835= (c.2505C>T)?

DOCK6 p.Tyr835= (c.2505C>T) is associated with Adams-Oliver syndrome 2 (ClinVar).

How common is DOCK6 p.Tyr835= (c.2505C>T) in the general population?

DOCK6 p.Tyr835= (c.2505C>T) is ultra-rare (popmax 0.0929%, nfe) (gnomAD).

DOCK6 p.Tyr835=

c.2505C>T · rs200378092 · VCV737455

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0929%, nfe)

Conditions

Adams-Oliver syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.44	GERP -5
Overall
CADD	2.754	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0929% European (non-Finnish) · 1,092/1,175,318 alleles

Filtering AF 0.0883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0865%

Overall 0.0724% 1,161/1,603,396 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0929%	1,076
Finnishnot grpmax-eligible	0.0412%	2,427
Remaining individualsnot grpmax-eligible	0.0354%	2,822
East Asian	0.018%	5,564
African / African-American	0.0147%	6,804
Admixed American	0.00342%	29,213

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.Tyr835=
Coding: c.2505C>T
MANE Select: NM_020812
dbSNP: rs200378092
Type: single nucleotide variant
Location: chr19:11235647 (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

Similar variants

DOCK6 p.Tyr835Ter Pathogenic ★ 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
DOCK6 p.Gln1188Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Tyr129Ter 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-tyr835 (accessed [today's date]).

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