Is DOCK3 p.Arg1609Trp (c.4825C>T) pathogenic?

DOCK3 p.Arg1609Trp (c.4825C>T) is classified Uncertain significance in DOCK3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-24). AlphaMissense: likely pathogenic (0.6413); Ultra-rare (popmax 0.0133%, afr); Associated with Inborn genetic diseases.

What condition is associated with DOCK3 p.Arg1609Trp (c.4825C>T)?

DOCK3 p.Arg1609Trp (c.4825C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK3 p.Arg1609Trp (c.4825C>T) in the general population?

DOCK3 p.Arg1609Trp (c.4825C>T) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about DOCK3 p.Arg1609Trp (c.4825C>T)?

AlphaMissense predicts likely pathogenic (score 0.6413) — an in-silico prediction, not a clinical call.

DOCK3 p.Arg1609Trp

c.4825C>T · rs372827222 · VCV977730

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6413 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6413	likely pathogenic
REVEL	0.594	indeterminate
SaProt	LLR -10.07	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP -1.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 154 kb · p 4e-32 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0133% African / African-American · 10/74,910 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000867% 14/1,613,852 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,491
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Admixed American	0.00167%	59,994
European (non-Finnish)	0.00017%	589,950

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.Arg1609Trp
Coding: c.4825C>T
MANE Select: NM_004947
dbSNP: rs372827222
Type: single nucleotide variant
Location: chr3:51358018 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 1609: a UniProt-annotated variant site (in nedidha); the docker domain

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.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
DOCK3 p.Lys343Arg Uncertain significance ★★ ⚠ same condition
DOCK3 p.Met1336Thr 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-arg1609trp (accessed [today's date]).

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