Is DOCK8 p.Arg18Lys (c.53G>A) pathogenic?

DOCK8 p.Arg18Lys (c.53G>A) is classified Uncertain significance in DOCK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). AlphaMissense: likely pathogenic (0.7607); Very rare (popmax 8.54e-05%, nfe).

How common is DOCK8 p.Arg18Lys (c.53G>A) in the general population?

DOCK8 p.Arg18Lys (c.53G>A) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

What do computational predictors say about DOCK8 p.Arg18Lys (c.53G>A)?

AlphaMissense predicts likely pathogenic (score 0.7607) — an in-silico prediction, not a clinical call.

DOCK8 p.Arg18Lys

c.53G>A · rs1197388365 · VCV1370037

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7607	likely pathogenic
REVEL	0.246	benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.30	loss · gain 0.01 · independent
Constraint at this position
Conservation	phyloP 9.5	GERP -0.075, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 235 kb · p 6.4e-14 · regional, not allelic
Overall
CADD	26.0	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 8.54e-05% European (non-Finnish) · 1/1,171,444 alleles

Overall 0.000657% 1/152,136 alleles · very rare

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.Arg18Lys
Coding: c.53G>A
dbSNP: rs1197388365
Type: single nucleotide variant
Location: chr9:215029 (GRCh38)

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

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-arg18lys (accessed [today's date]).

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