Is DOCK6 p.Glu617Lys (c.1849G>A) pathogenic?

DOCK6 p.Glu617Lys (c.1849G>A) is classified Uncertain significance in DOCK6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-02). AlphaMissense: likely pathogenic (0.6443); Ultra-rare (popmax 0.05%, afr).

How common is DOCK6 p.Glu617Lys (c.1849G>A) in the general population?

DOCK6 p.Glu617Lys (c.1849G>A) is ultra-rare (popmax 0.05%, afr) (gnomAD).

What do computational predictors say about DOCK6 p.Glu617Lys (c.1849G>A)?

AlphaMissense predicts likely pathogenic (score 0.6443) — an in-silico prediction, not a clinical call.

DOCK6 p.Glu617Lys

c.1849G>A · rs367747093 · VCV1403326

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6443 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.05%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6443	likely pathogenic
REVEL	0.531	indeterminate
SaProt	LLR -12.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.05% African / African-American · 37/73,960 alleles

Filtering AF 0.0373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0329%

Overall 0.00299% 47/1,569,580 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.05%	1,999
Admixed American	0.0114%	8,788
Remaining individualsnot grpmax-eligible	0.00656%	15,239

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.Glu617Lys
Coding: c.1849G>A
MANE Select: NM_020812
dbSNP: rs367747093
Type: single nucleotide variant
Location: chr19:11237763 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 617: the c2 dock-type domain

Full DOCK6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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
DOCK6 p.Arg488Ter Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Gln1188Ter Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Glu1494Ter 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-glu617lys (accessed [today's date]).

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