Is DOCK5 p.Gln206Arg (c.617A>G) pathogenic?

DOCK5 p.Gln206Arg (c.617A>G) is classified Uncertain significance in DOCK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.1105); Ultra-rare (popmax 0.033%, mid).

How common is DOCK5 p.Gln206Arg (c.617A>G) in the general population?

DOCK5 p.Gln206Arg (c.617A>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about DOCK5 p.Gln206Arg (c.617A>G)?

AlphaMissense predicts likely benign (score 0.1105) — an in-silico prediction, not a clinical call.

DOCK5 p.Gln206Arg

c.617A>G · VCV4243939

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1105 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1105	likely benign
REVEL	0.713	pathogenic-leaning
SaProt	LLR -7.17	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 116 kb · p 0.58 · regional, not allelic
Overall
CADD	21.3	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 0.033% Middle Eastern · 2/6,056 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000682% 11/1,612,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,028
African / African-American	0.0107%	9,370
Remaining individualsnot grpmax-eligible	0.0016%	62,396

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: DOCK5
Protein: p.Gln206Arg
Coding: c.617A>G
MANE Select: NM_024940
Type: single nucleotide variant
Location: chr8:25298954 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 11 PDB

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-gln206arg (accessed [today's date]).

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