Is DOCK5 p.Glu596Gln (c.1786G>C) pathogenic?

DOCK5 p.Glu596Gln (c.1786G>C) is classified Uncertain significance in DOCK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.1165); Absent from gnomAD v4.1.

How common is DOCK5 p.Glu596Gln (c.1786G>C) in the general population?

DOCK5 p.Glu596Gln (c.1786G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK5 p.Glu596Gln (c.1786G>C)?

AlphaMissense predicts likely benign (score 0.1165) — an in-silico prediction, not a clinical call.

DOCK5 p.Glu596Gln

c.1786G>C · rs375695909 · VCV3085032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1165 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1165	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 107 kb · p 5.5e-05 · regional, not allelic
Overall
CADD	24.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOCK5
Protein: p.Glu596Gln
Coding: c.1786G>C
MANE Select: NM_024940
dbSNP: rs375695909
Type: single nucleotide variant
Location: chr8:25325430 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 11 PDB
Residue 596: the c2 dock-type domain

Full DOCK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK5 c.4788+9C>T Benign ★★ same type
DOCK5 p.Leu986Phe Benign/Likely benign ★★ same type
DOCK5 p.Met987Leu Benign ★★ same type
DOCK5 p.Pro1467= Benign ★★ same type
DOCK5 p.Ser1306= Benign ★★ same type
DOCK5 p.Thr469Met Benign/Likely benign ★★ ⚠ same type
DOCK5 p.Ala1067Val Uncertain significance ★ ⚠ same type
DOCK5 p.Ala1194Ser Uncertain significance ★ ⚠ same type

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/dock5-p-glu596gln (accessed [today's date]).

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