Is DOCK8 p.Phe12Val (c.34T>G) pathogenic?

DOCK8 p.Phe12Val (c.34T>G) is classified Uncertain significance in DOCK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.8861); Very rare (popmax 0.00102%, nfe); Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Phe12Val (c.34T>G)?

DOCK8 p.Phe12Val (c.34T>G) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Phe12Val (c.34T>G) in the general population?

DOCK8 p.Phe12Val (c.34T>G) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about DOCK8 p.Phe12Val (c.34T>G)?

AlphaMissense predicts likely pathogenic (score 0.8861) — an in-silico prediction, not a clinical call.

DOCK8 p.Phe12Val

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

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

c.34T>G · rs886063779 · VCV366227

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8861 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined immunodeficiency due to DOCK8 deficiency

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.8861	likely pathogenic
REVEL	0.226	benign-leaning
SaProt	LLR -5.11	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 0.48, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 235 kb · p 6.4e-14 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,174,808 alleles

Filtering AF 0.000545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00043%

Overall 0.000753% 12/1,592,916 alleles · very rare exomes 11/1,440,794 · genomes 1/152,122 · joint denominator

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.Phe12Val
Coding: c.34T>G
MANE Select: NM_203447
dbSNP: rs886063779
Type: single nucleotide variant
Location: chr9:215010 (GRCh38)

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

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-phe12val (accessed [today's date]).

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