Is DOCK6 p.Ala833Asp (c.2498C>A) pathogenic?

DOCK6 p.Ala833Asp (c.2498C>A) is classified Uncertain significance in DOCK6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-30). AlphaMissense: ambiguous (0.437); Very rare (popmax 0.00825%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Ala833Asp (c.2498C>A)?

DOCK6 p.Ala833Asp (c.2498C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Ala833Asp (c.2498C>A) in the general population?

DOCK6 p.Ala833Asp (c.2498C>A) is very rare (popmax 0.00825%, nfe) (gnomAD).

What do computational predictors say about DOCK6 p.Ala833Asp (c.2498C>A)?

AlphaMissense predicts ambiguous (score 0.437) — an in-silico prediction, not a clinical call.

DOCK6 p.Ala833Asp

c.2498C>A · rs773345225 · VCV1001046

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.437 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00825%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.437	ambiguous
REVEL	0.299	indeterminate
SaProt	LLR -7.23	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	24.1	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 0.00825% European (non-Finnish) · 97/1,175,356 alleles

Filtering AF 0.00692% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00636%

Overall 0.00624% 100/1,603,298 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00825%	12,117
African / African-American	0.00268%	37,374
Remaining individualsnot grpmax-eligible	0.00161%	62,040

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.Ala833Asp
Coding: c.2498C>A
MANE Select: NM_020812
dbSNP: rs773345225
Type: single nucleotide variant
Location: chr19:11235654 (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 p.Ala833Val Uncertain significance ★ ⚠ 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
DOCK6 p.Ala133Thr 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-ala833asp (accessed [today's date]).

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