Is DOCK9 p.Arg1069His (c.3206G>A) pathogenic?

DOCK9 p.Arg1069His (c.3206G>A) is classified Uncertain significance in DOCK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely benign (0.136); Ultra-rare (popmax 0.0165%, mid).

How common is DOCK9 p.Arg1069His (c.3206G>A) in the general population?

DOCK9 p.Arg1069His (c.3206G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DOCK9 p.Arg1069His (c.3206G>A)?

AlphaMissense predicts likely benign (score 0.136) — an in-silico prediction, not a clinical call.

DOCK9 p.Arg1069His

c.3206G>A · rs370027438 · VCV2217317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.136 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.136	likely benign
REVEL	0.66	pathogenic-leaning
SaProt	LLR -5.73	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.67 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 0.92, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 140 kb · p 1.2e-07 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1070H vs ClinVar R1069H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00425% 62/1,458,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
Finnishnot grpmax-eligible	0.00469%	21,308
European (non-Finnish)	0.00467%	21,429
Admixed American	0.00337%	29,683
Remaining individualsnot grpmax-eligible	0.0016%	62,330

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: DOCK9
Protein: p.Arg1069His
Coding: c.3206G>A
MANE Select: NM_001366683
dbSNP: rs370027438
Type: single nucleotide variant
Location: chr13:98867505 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68 · 4 PDB

Full DOCK9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK9 p.Ala434Val Benign ★★ same type
DOCK9 p.Asn1709= Benign ★★ same type
DOCK9 p.Cys2012= Benign/Likely benign ★★ same type
DOCK9 p.Leu1435= Benign ★★ same type
DOCK9 c.5023+908C>T Uncertain significance ★ ⚠ same type
DOCK9 c.5023+919C>T Uncertain significance ★ ⚠ same type
DOCK9 c.5023+952C>T Uncertain significance ★ ⚠ same type
DOCK9 c.5367+706T>A 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/dock9-p-arg1069his (accessed [today's date]).

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