Is DOCK3 p.Arg2005Cys (c.6013C>T) pathogenic?

DOCK3 p.Arg2005Cys (c.6013C>T) is classified Uncertain significance in DOCK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.2234); Very rare (popmax 0.00316%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK3 p.Arg2005Cys (c.6013C>T)?

DOCK3 p.Arg2005Cys (c.6013C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK3 p.Arg2005Cys (c.6013C>T) in the general population?

DOCK3 p.Arg2005Cys (c.6013C>T) is very rare (popmax 0.00316%, nfe) (gnomAD).

What do computational predictors say about DOCK3 p.Arg2005Cys (c.6013C>T)?

AlphaMissense predicts likely benign (score 0.2234) — an in-silico prediction, not a clinical call.

DOCK3 p.Arg2005Cys

c.6013C>T · rs375293337 · VCV2257569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2234 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00316%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2234	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -9.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 310 bp · p 0.72 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00316% European (non-Finnish) · 37/1,169,240 alleles

Filtering AF 0.00233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00204%

Overall 0.00245% 39/1,590,140 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00316%	31,601
African / African-American	0.00269%	37,186

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: DOCK3
Protein: p.Arg2005Cys
Coding: c.6013C>T
MANE Select: NM_004947
dbSNP: rs375293337
Type: single nucleotide variant
Location: chr3:51381479 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 2005: a UniProt-annotated variant site (in nedidha); the 'disordered' region

Full DOCK3 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

DOCK3 p.Arg2005His Uncertain significance ★ ⚠ same residue
DOCK3 p.Arg1609Trp Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg1787Gln Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg2020Cys Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg392Gln Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg486His Uncertain significance ★★ ⚠ same condition
DOCK3 p.Gly1699Cys Uncertain significance ★★ ⚠ same condition
DOCK3 p.Leu1982Arg 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/dock3-p-arg2005cys (accessed [today's date]).

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