Is DOCK9 p.Arg984Gln (c.2951G>A) pathogenic?

DOCK9 p.Arg984Gln (c.2951G>A) is classified Uncertain significance in DOCK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely pathogenic (0.9378); Very rare (popmax 0.00338%, amr).

How common is DOCK9 p.Arg984Gln (c.2951G>A) in the general population?

DOCK9 p.Arg984Gln (c.2951G>A) is very rare (popmax 0.00338%, amr) (gnomAD).

What do computational predictors say about DOCK9 p.Arg984Gln (c.2951G>A)?

AlphaMissense predicts likely pathogenic (score 0.9378) — an in-silico prediction, not a clinical call.

DOCK9 p.Arg984Gln

c.2951G>A · rs1323738459 · VCV3085125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9378 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00338%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9378	likely pathogenic
REVEL	0.381	indeterminate
SaProt	LLR -11.39	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 140 kb · p 1.2e-07 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R985Q vs ClinVar R984Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00338% Admixed American · 2/59,148 alleles

Filtering AF 0.000561% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00021%

Overall 0.00048% 7/1,457,586 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00338%	29,574
Remaining individualsnot grpmax-eligible	0.0016%	62,372
European (non-Finnish)	0.000339%	294,590

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.Arg984Gln
Coding: c.2951G>A
MANE Select: NM_001366683
dbSNP: rs1323738459
Type: single nucleotide variant
Location: chr13:98868370 (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-arg984gln (accessed [today's date]).

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