Is DOCK3 p.Arg2001Ter (c.6001C>T) pathogenic?

DOCK3 p.Arg2001Ter (c.6001C>T) is classified Likely pathogenic in DOCK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). Very rare (popmax 0.00456%, eas); Associated with neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia.

How common is DOCK3 p.Arg2001Ter (c.6001C>T) in the general population?

DOCK3 p.Arg2001Ter (c.6001C>T) is very rare (popmax 0.00456%, eas) (gnomAD).

DOCK3 p.Arg2001Ter

Q: What condition is associated with DOCK3 p.Arg2001Ter (c.6001C>T)?

DOCK3 p.Arg2001Ter (c.6001C>T) is associated with neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia (ClinVar).

c.6001C>T · VCV4849416

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00456%, eas)

Conditions

neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (53 of 53) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -2.5, phastCons 0.97
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00456% East Asian · 2/43,834 alleles

Filtering AF 0.000756% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000283%

Overall 0.000346% 5/1,444,522 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00456%	21,917
South Asian	0.00224%	44,641
European (non-Finnish)	8.53e-05%	1,172,362

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.Arg2001Ter
Coding: c.6001C>T
MANE Select: NM_004947
Type: single nucleotide variant
Location: chr3:51381467 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 2001: 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

neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK3 p.Arg392Gln Uncertain significance ★★ ⚠ same condition
DOCK3 p.Lys1296Arg Uncertain significance ★★ ⚠ same condition
DOCK3 p.Val148Met Uncertain significance ★★ ⚠ same condition
DOCK3 p.Val668Met Uncertain significance ★★ ⚠ same condition
DOCK3 c.1918-3T>C Benign ★★ same condition
DOCK3 c.1038-2A>G Likely pathogenic ★ same condition
DOCK3 p.Gln128Ter Pathogenic ★ same condition
DOCK3 p.Arg741Trp 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-arg2001ter (accessed [today's date]).

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