Is DOCK6 p.Val263Asp (c.788T>A) pathogenic?

DOCK6 p.Val263Asp (c.788T>A) is classified Pathogenic in DOCK6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-01). AlphaMissense: likely pathogenic (0.9989); Absent from gnomAD v4.1; Associated with Adams-Oliver syndrome 2.

What condition is associated with DOCK6 p.Val263Asp (c.788T>A)?

DOCK6 p.Val263Asp (c.788T>A) is associated with Adams-Oliver syndrome 2 (ClinVar).

How common is DOCK6 p.Val263Asp (c.788T>A) in the general population?

DOCK6 p.Val263Asp (c.788T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK6 p.Val263Asp (c.788T>A)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

DOCK6 p.Val263Asp

c.788T>A · rs879255610 · VCV253046

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Adams-Oliver syndrome 2

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic ✓ concordant with ClinVar · top 1% in DOCK6
REVEL	0.738	pathogenic-leaning
SaProt	LLR -18.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOCK6
Protein: p.Val263Asp
Coding: c.788T>A
MANE Select: NM_020812
dbSNP: rs879255610
Type: single nucleotide variant
Location: chr19:11248084 (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 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
DOCK6 p.Tyr235Ter 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-val263asp (accessed [today's date]).

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