Is DOCK6 p.Ala243Asp (c.728C>A) pathogenic?

DOCK6 p.Ala243Asp (c.728C>A) is classified Uncertain significance in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: ambiguous (0.3846); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Ala243Asp (c.728C>A)?

DOCK6 p.Ala243Asp (c.728C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Ala243Asp (c.728C>A) in the general population?

DOCK6 p.Ala243Asp (c.728C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK6 p.Ala243Asp (c.728C>A)?

AlphaMissense predicts ambiguous (score 0.3846) — an in-silico prediction, not a clinical call.

DOCK6 p.Ala243Asp

c.728C>A · rs772708645 · VCV2274009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3846 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,274)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3846	ambiguous
REVEL	0.178	moderately benign-leaning
SaProt	LLR -6.59	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	23.2	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

No allele count reported in gnomAD v4.1 (AN 1,607,274). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DOCK6
Protein: p.Ala243Asp
Coding: c.728C>A
MANE Select: NM_020812
dbSNP: rs772708645
Type: single nucleotide variant
Location: chr19:11248144 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 243: the 'disordered' region

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 p.Ala243Val Uncertain significance ★ ⚠ same residue
DOCK6 p.Ala243= Likely benign ★★ same residue
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

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-ala243asp (accessed [today's date]).

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