Is DOCK6 p.Pro502Leu (c.1505C>T) pathogenic?

DOCK6 p.Pro502Leu (c.1505C>T) is classified Uncertain significance in DOCK6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-25). AlphaMissense: likely pathogenic (0.6991); Ultra-rare (popmax 0.0148%, eas); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Pro502Leu (c.1505C>T)?

DOCK6 p.Pro502Leu (c.1505C>T) is associated with Inborn genetic diseases, Adams-Oliver syndrome 2 (ClinVar).

How common is DOCK6 p.Pro502Leu (c.1505C>T) in the general population?

DOCK6 p.Pro502Leu (c.1505C>T) is ultra-rare (popmax 0.0148%, eas) (gnomAD).

What do computational predictors say about DOCK6 p.Pro502Leu (c.1505C>T)?

AlphaMissense predicts likely pathogenic (score 0.6991) — an in-silico prediction, not a clinical call.

DOCK6 p.Pro502Leu

c.1505C>T · VCV3273389

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6991 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6991	likely pathogenic
REVEL	0.398	indeterminate
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	27.3	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 0.0148% East Asian · 6/40,468 alleles

Filtering AF 0.00641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00438%

Overall 0.000955% 14/1,465,444 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0148%	6,745
African / African-American	0.00428%	23,344
Admixed American	0.00267%	37,512
Remaining individualsnot grpmax-eligible	0.00179%	56,006
European (non-Finnish)	0.00027%	370,226

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.Pro502Leu
Coding: c.1505C>T
MANE Select: NM_020812
Type: single nucleotide variant
Location: chr19:11242183 (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

Also linked: Adams-Oliver syndrome 2

Similar variants

DOCK6 p.Pro502= Likely benign ★ same residue
DOCK6 c.5939+2T>C Pathogenic ★★ same condition
DOCK6 c.807-1G>A Likely pathogenic ★★ same condition
DOCK6 p.Arg1526Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Arg184Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Arg488Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Gln1188Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Glu1494Ter Pathogenic ★★ 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-pro502leu (accessed [today's date]).

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