Is DOCK3 p.Arg140Trp (c.418C>T) pathogenic?

DOCK3 p.Arg140Trp (c.418C>T) is classified Uncertain significance in DOCK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: ambiguous (0.3857); Very rare (popmax 0.00988%, sas); Associated with Inborn genetic diseases.

What condition is associated with DOCK3 p.Arg140Trp (c.418C>T)?

DOCK3 p.Arg140Trp (c.418C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK3 p.Arg140Trp (c.418C>T) in the general population?

DOCK3 p.Arg140Trp (c.418C>T) is very rare (popmax 0.00988%, sas) (gnomAD).

What do computational predictors say about DOCK3 p.Arg140Trp (c.418C>T)?

AlphaMissense predicts ambiguous (score 0.3857) — an in-silico prediction, not a clinical call.

DOCK3 p.Arg140Trp

c.418C>T · VCV4014113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3857 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3857	ambiguous
REVEL	0.423	indeterminate
SaProt	LLR -9.32	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.9	GERP 0.74, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 550 kb · p 0.00035 · regional, not allelic
Overall
CADD	28.0	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 0.00988% South Asian · 9/91,080 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.000889% 13/1,461,654 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,120
East Asian	0.00668%	14,960
European (non-Finnish)	8.48e-05%	1,179,839

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.Arg140Trp
Coding: c.418C>T
MANE Select: NM_004947
Type: single nucleotide variant
Location: chr3:51064550 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 140: a UniProt-annotated variant site (in nedidha)

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.Arg140Leu 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-arg140trp (accessed [today's date]).

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