Is DOCK8 p.Asp1413fs (c.4235dup) pathogenic?

DOCK8 p.Asp1413fs (c.4235dup) is classified Pathogenic in DOCK8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-09). Very rare (popmax 0.00246%, nfe); Associated with DOCK8-related disorders.

What condition is associated with DOCK8 p.Asp1413fs (c.4235dup)?

DOCK8 p.Asp1413fs (c.4235dup) is associated with DOCK8-related disorders, combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Asp1413fs (c.4235dup) in the general population?

DOCK8 p.Asp1413fs (c.4235dup) is very rare (popmax 0.00246%, nfe) (gnomAD).

DOCK8 p.Asp1413fs

c.4235dup · rs1486504113 · VCV2136721

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Conditions

DOCK8-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 33 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -0.87, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,179,938 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00192% 31/1,613,856 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)grpmax	0.00246%	40,687

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: DOCK8
Protein: p.Asp1413fs
Coding: c.4235dup
MANE Select: NM_203447
dbSNP: rs1486504113
Type: Duplication
Location: chr9:422128 (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

DOCK8-related disorders

Also linked: combined immunodeficiency due to DOCK8 deficiency

Similar variants

DOCK8 p.Leu1059fs Pathogenic/Likely pathogenic ★★ same condition
DOCK8 p.Tyr2007fs Pathogenic ★★ same condition
DOCK8 c.3234+15dup Benign ★★ same condition
DOCK8 c.3234+21dup Benign/Likely benign ★★ same condition
DOCK8 p.Ala1170fs Pathogenic ★ same condition
DOCK8 p.Arg1828Ter Pathogenic ★ same condition
DOCK8 p.Asn1395fs Likely pathogenic ★ same condition
DOCK8 p.Glu1680fs Pathogenic ★ 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-p-asp1413fs (accessed [today's date]).

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