Is DOCK9 p.Cys2012= (c.6036C>T) pathogenic?

DOCK9 p.Cys2012= (c.6036C>T) is classified Benign/Likely benign in DOCK9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-01). Rare (popmax 0.742%, mid).

How common is DOCK9 p.Cys2012= (c.6036C>T) in the general population?

DOCK9 p.Cys2012= (c.6036C>T) is rare (popmax 0.742%, mid) (gnomAD).

DOCK9 p.Cys2012=

c.6036C>T · rs41279128 · VCV790370

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.742%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.208	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -5.5
Overall
CADD	0.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.742% Middle Eastern · 45/6,062 alleles

Filtering AF 0.602% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.597%

Overall 0.547% 8,835/1,613,846 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.08%	48
Middle Easterngrpmax	0.742%	135
European (non-Finnish)	0.614%	163
Finnishnot grpmax-eligible	0.586%	171
Remaining individualsnot grpmax-eligible	0.586%	171
Admixed American	0.537%	186
South Asian	0.304%	329
Ashkenazi Jewishnot grpmax-eligible	0.226%	442
African / African-American	0.165%	605
East Asian	0.00223%	44,884

Amish 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.Cys2012=
Coding: c.6036C>T
MANE Select: NM_001366683
dbSNP: rs41279128
Type: single nucleotide variant
Location: chr13:98797235 (GRCh38)
Gene constraint: LOEUF 0.425 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.68 · 4 PDB
Residue 2012: the docker domain; the 'interaction with cdc42' region

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.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
DOCK9 p.Ala100Ser 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-cys2012 (accessed [today's date]).

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