Is DOCK9 p.Glu2020Lys (c.6058G>A) pathogenic?

DOCK9 p.Glu2020Lys (c.6058G>A) is classified Uncertain significance in DOCK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: ambiguous (0.5329); Very rare (popmax 0.00134%, afr).

How common is DOCK9 p.Glu2020Lys (c.6058G>A) in the general population?

DOCK9 p.Glu2020Lys (c.6058G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DOCK9 p.Glu2020Lys (c.6058G>A)?

AlphaMissense predicts ambiguous (score 0.5329) — an in-silico prediction, not a clinical call.

DOCK9 p.Glu2020Lys

c.6058G>A · rs2089528419 · VCV2557418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
AlphaMissense	0.5329	ambiguous
REVEL	0.355	indeterminate
SaProt	LLR -8.57	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 43 kb · p 1.3e-16 · regional, not allelic
Overall
CADD	24.5	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 E2035K vs ClinVar E2020K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,888 alleles

Overall 0.000186% 3/1,613,778 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,464
African / African-Americangrpmax	0.00134%	74,888
European (non-Finnish)	8.48e-05%	1,179,884

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu2020Lys
Coding: c.6058G>A
MANE Select: NM_001366683
dbSNP: rs2089528419
Type: single nucleotide variant
Location: chr13:98797213 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68 · 4 PDB
Residue 2020: the docker domain; the 'interaction with cdc42' region; an α-helix

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-glu2020lys (accessed [today's date]).

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