Is DOCK6 p.Arg1305Cys (c.3913C>T) pathogenic?

DOCK6 p.Arg1305Cys (c.3913C>T) is classified Benign/Likely benign in DOCK6 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-31). AlphaMissense: likely pathogenic (0.6381); Low-frequency (popmax 1.07%, nfe); Associated with Adams-Oliver syndrome 2.

What condition is associated with DOCK6 p.Arg1305Cys (c.3913C>T)?

DOCK6 p.Arg1305Cys (c.3913C>T) is associated with Adams-Oliver syndrome 2 (ClinVar).

How common is DOCK6 p.Arg1305Cys (c.3913C>T) in the general population?

DOCK6 p.Arg1305Cys (c.3913C>T) is low-frequency (popmax 1.07%, nfe) (gnomAD).

What do computational predictors say about DOCK6 p.Arg1305Cys (c.3913C>T)?

AlphaMissense predicts likely pathogenic (score 0.6381) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg1305Cys

c.3913C>T · rs112911897 · VCV445548

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.6381 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Adams-Oliver syndrome 2

Computational evidence

Protein change
AlphaMissense	0.6381	likely pathogenic
REVEL	0.212	benign-leaning
SaProt	LLR -10.31	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.9	GERP 0.11, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	27.6	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

Grpmax group 1.07% European (non-Finnish) · 12,576/1,179,836 alleles

Filtering AF 1.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.04%

Overall 0.972% 15,686/1,613,744 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.41%	42
European (non-Finnish)grpmax	1.07%	94
South Asian	0.794%	126
Remaining individualsnot grpmax-eligible	0.744%	134
Admixed American	0.325%	308
Ashkenazi Jewishnot grpmax-eligible	0.26%	385
African / African-American	0.139%	721
Middle Eastern	0.099%	1,010

Finnish 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.Arg1305Cys
Coding: c.3913C>T
MANE Select: NM_020812
dbSNP: rs112911897
Type: single nucleotide variant
Location: chr19:11215909 (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.Arg1305His Uncertain significance ★★ ⚠ 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-arg1305cys (accessed [today's date]).

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