Is DOCK8 c.53+14del pathogenic?

DOCK8 c.53+14del is classified Benign/Likely benign in DOCK8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-22). Ultra-rare (popmax 0.0183%, sas); Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 c.53+14del?

DOCK8 c.53+14del is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 c.53+14del in the general population?

DOCK8 c.53+14del is ultra-rare (popmax 0.0183%, sas) (gnomAD).

DOCK8 c.53+14del

Q: How is Combined immunodeficiency due to DOCK8 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

rs749863710 · VCV1167043

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, sas)

Conditions

combined immunodeficiency due to DOCK8 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +14	near-intronic (+14 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.86	GERP -1.2, phastCons 0.009
Overall
CADD	12.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% South Asian · 16/87,404 alleles

Filtering AF 0.0114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00933%

Overall 0.00184% 29/1,572,678 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0183%	5,463
Remaining individualsnot grpmax-eligible	0.0049%	20,395
East Asian	0.0047%	21,265
African / African-American	0.00277%	36,063
Admixed American	0.00176%	56,680
European (non-Finnish)	0.000428%	233,463

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: DOCK8
Coding: c.53+14del
MANE Select: NM_203447
dbSNP: rs749863710
Type: Deletion
Location: chr9:215038 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17

Full DOCK8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined immunodeficiency due to DOCK8 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to DOCK8 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DOCK8 p.Leu1754fs Pathogenic ★★ same condition
DOCK8 p.Phe1113fs Pathogenic/Likely pathogenic ★★ same condition
DOCK8 p.Tyr491fs Pathogenic ★★ same condition
DOCK8 c.2109+11del Benign/Likely benign ★★ same condition
DOCK8 c.3234+15del Benign/Likely benign ★★ same condition
DOCK8 c.3234+8del Benign ★★ same condition
DOCK8 c.333-8del Likely benign ★★ same condition
DOCK8 c.404+16del Benign/Likely benign ★★ 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/dock8-c-53-plus-14del (accessed [today's date]).

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