Is DOCK2 p.Thr405= (c.1215C>T) pathogenic?

DOCK2 p.Thr405= (c.1215C>T) is classified Likely benign in DOCK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-23). Rare (popmax 0.136%, afr); Associated with Inborn genetic diseases.

What condition is associated with DOCK2 p.Thr405= (c.1215C>T)?

DOCK2 p.Thr405= (c.1215C>T) is associated with Inborn genetic diseases, DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Thr405= (c.1215C>T) in the general population?

DOCK2 p.Thr405= (c.1215C>T) is rare (popmax 0.136%, afr) (gnomAD).

DOCK2 p.Thr405=

c.1215C>T · rs141406325 · VCV542621

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.136%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.8
Overall
CADD	1.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.136% African / African-American · 102/75,040 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.107%

Overall 0.00867% 140/1,613,944 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.136%	736
Middle Eastern	0.033%	3,028
East Asian	0.029%	3,452
Remaining individualsnot grpmax-eligible	0.0128%	7,812
Admixed American	0.005%	20,004
South Asian	0.0011%	91,060
European (non-Finnish)	0.000932%	107,261

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: DOCK2
Protein: p.Thr405=
Coding: c.1215C>T
MANE Select: NM_004946
dbSNP: rs141406325
Type: single nucleotide variant
Location: chr5:169700096 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB

Full DOCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: DOCK2 deficiency

Similar variants

DOCK2 p.Thr405Ala Uncertain significance ★ same residue
INSYN2B p.Ala405Val Uncertain significance ★ ⚠ same residue
DOCK2 c.2267+3G>A Uncertain significance ★★ same condition
DOCK2 c.2704-3C>T Uncertain significance ★★ same condition
DOCK2 c.4467+4A>G Uncertain significance ★★ same condition
DOCK2 p.Ala1393Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1710Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1765Val Uncertain significance ★★ ⚠ same condition

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/dock2-p-thr405 (accessed [today's date]).

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