Is DOCK6 p.Glu77Lys (c.229G>A) pathogenic?

DOCK6 p.Glu77Lys (c.229G>A) is classified Uncertain significance in DOCK6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-27). AlphaMissense: ambiguous (0.4397); Rare (popmax 0.104%, afr); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Glu77Lys (c.229G>A)?

DOCK6 p.Glu77Lys (c.229G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Glu77Lys (c.229G>A) in the general population?

DOCK6 p.Glu77Lys (c.229G>A) is rare (popmax 0.104%, afr) (gnomAD).

What do computational predictors say about DOCK6 p.Glu77Lys (c.229G>A)?

AlphaMissense predicts ambiguous (score 0.4397) — an in-silico prediction, not a clinical call.

DOCK6 p.Glu77Lys

c.229G>A · rs368217762 · VCV1394811

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4397 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.104%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4397	ambiguous
REVEL	0.15	moderately benign-leaning
SaProt	LLR -6.09	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.27	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	26.7	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 0.104% African / African-American · 78/74,924 alleles

Filtering AF 0.0855% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0786%

Overall 0.00533% 86/1,613,788 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.104%	961
Middle Eastern	0.0164%	6,082
Admixed American	0.00833%	11,998
Remaining individualsnot grpmax-eligible	0.0016%	62,458
South Asian	0.0011%	91,088

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.Glu77Lys
Coding: c.229G>A
MANE Select: NM_020812
dbSNP: rs368217762
Type: single nucleotide variant
Location: chr19:11252862 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK6 c.5939+2T>C Pathogenic ★★ same condition
DOCK6 p.Glu1494Ter Pathogenic ★★ same condition
DOCK6 p.Ala1153Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1207Val Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1241Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1319Val Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala133Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1481Thr Uncertain significance ★★ ⚠ 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-glu77lys (accessed [today's date]).

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