Is DOCK3 p.Pro1406fs (c.4217del) pathogenic?

DOCK3 p.Pro1406fs (c.4217del) is classified Pathogenic/Likely pathogenic in DOCK3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). Absent from gnomAD; Associated with neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia.

How common is DOCK3 p.Pro1406fs (c.4217del) in the general population?

DOCK3 p.Pro1406fs (c.4217del) is absent from gnomAD (gnomAD).

DOCK3 p.Pro1406fs

Q: What condition is associated with DOCK3 p.Pro1406fs (c.4217del)?

DOCK3 p.Pro1406fs (c.4217del) is associated with neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia (ClinVar).

c.4217del · rs2549285187 · VCV2634425

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 41 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.41	GERP -5.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DOCK3
Protein: p.Pro1406fs
Coding: c.4217del
MANE Select: NM_004947
dbSNP: rs2549285187
Type: Deletion
Location: chr3:51354990 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 1406: 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

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

Similar variants

DOCK3 p.Leu1411fs Pathogenic ★ same condition
DOCK3 p.Tyr1036fs Pathogenic same condition
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

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-pro1406fs (accessed [today's date]).

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