Is DOCK6 p.Arg1228Trp (c.3682C>T) pathogenic?

DOCK6 p.Arg1228Trp (c.3682C>T) is classified Uncertain significance in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.1701); Very rare (popmax 0.0033%, sas).

How common is DOCK6 p.Arg1228Trp (c.3682C>T) in the general population?

DOCK6 p.Arg1228Trp (c.3682C>T) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about DOCK6 p.Arg1228Trp (c.3682C>T)?

AlphaMissense predicts likely benign (score 0.1701) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg1228Trp

c.3682C>T · rs770733247 · VCV1985844

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1701 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1701	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.91, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/90,894 alleles

Filtering AF 0.000877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00093% 15/1,612,544 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,298
Remaining individualsnot grpmax-eligible	0.0032%	31,205
Admixed American	0.00167%	59,868
African / African-American	0.00133%	74,916
European (non-Finnish)	0.000678%	147,447

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.Arg1228Trp
Coding: c.3682C>T
MANE Select: NM_020812
dbSNP: rs770733247
Type: single nucleotide variant
Location: chr19:11217260 (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

Similar variants

DOCK6 p.Arg1228Gln Uncertain significance ★ ⚠ same residue
DOCK6 p.Arg1228= Likely benign ★ same residue
DOCK6 p.Arg1228fs Pathogenic ★ same residue
DOCK6 c.4491+1G>A Pathogenic ★★ same type
DOCK6 c.5939+2T>C Pathogenic ★★ same type
DOCK6 c.807-1G>A Likely pathogenic ★★ same type
DOCK6 p.Arg1526Ter Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Arg184Ter Pathogenic/Likely pathogenic ★★ same type

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-arg1228trp (accessed [today's date]).

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