Is DOCK8 p.Pro5Arg (c.14C>G) pathogenic?

DOCK8 p.Pro5Arg (c.14C>G) is classified Uncertain significance in DOCK8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-13). AlphaMissense: ambiguous (0.4892); Very rare (popmax 0.00112%, sas); Associated with Inborn genetic diseases.

What condition is associated with DOCK8 p.Pro5Arg (c.14C>G)?

DOCK8 p.Pro5Arg (c.14C>G) is associated with Inborn genetic diseases, combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Pro5Arg (c.14C>G) in the general population?

DOCK8 p.Pro5Arg (c.14C>G) is very rare (popmax 0.00112%, sas) (gnomAD).

What do computational predictors say about DOCK8 p.Pro5Arg (c.14C>G)?

AlphaMissense predicts ambiguous (score 0.4892) — an in-silico prediction, not a clinical call.

DOCK8 p.Pro5Arg

c.14C>G · rs1018736787 · VCV2192847

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4892 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4892	ambiguous
REVEL	0.232	benign-leaning
SaProt	LLR -5.67	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 235 kb · p 6.4e-14 · regional, not allelic
Overall
CADD	24.3	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 0.00112% South Asian · 1/89,578 alleles

Filtering AF 0.00043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00076% 11/1,446,806 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00112%	89,578
European (non-Finnish)	0.00085%	117,626

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.Pro5Arg
Coding: c.14C>G
dbSNP: rs1018736787
Type: single nucleotide variant
Location: chr9:214990 (GRCh38)

Full DOCK8 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: combined immunodeficiency due to DOCK8 deficiency

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-pro5arg (accessed [today's date]).

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