Is DOCK8 p.Met2022Val (c.6064A>G) pathogenic?

DOCK8 p.Met2022Val (c.6064A>G) is classified Conflicting classifications of pathogenicity in DOCK8 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-10-16). AlphaMissense: likely benign (0.121); Rare (popmax 0.133%, mid).

How common is DOCK8 p.Met2022Val (c.6064A>G) in the general population?

DOCK8 p.Met2022Val (c.6064A>G) is rare (popmax 0.133%, mid) (gnomAD).

What do computational predictors say about DOCK8 p.Met2022Val (c.6064A>G)?

AlphaMissense predicts likely benign (score 0.121) — an in-silico prediction, not a clinical call.

DOCK8 p.Met2022Val

c.6064A>G · rs143458628 · VCV1059642

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.121 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.133%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.121	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -5.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 0.26, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 12 kb · p 0.6 · regional, not allelic
Overall
CADD	19.69	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 0.133% Middle Eastern · 8/6,032 alleles

Filtering AF 0.0659% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0481%

Overall 0.0143% 230/1,605,746 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.133%	754
European (non-Finnish)	0.018%	5,561
Admixed American	0.00835%	11,976
Remaining individualsnot grpmax-eligible	0.00804%	12,440
South Asian	0.0011%	90,740

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.Met2022Val
Coding: c.6064A>G
MANE Select: NM_203447
dbSNP: rs143458628
Type: single nucleotide variant
Location: chr9:452113 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17
Residue 2022: the docker domain

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

Similar variants

DOCK8 c.1680-2A>G Likely pathogenic ★★ same type
DOCK8 c.2779-2A>C Likely pathogenic ★★ same type
DOCK8 c.2971-1G>A Pathogenic ★★ same type
DOCK8 c.3530+1G>A Likely pathogenic ★★ same type
DOCK8 c.528+1G>A Likely pathogenic ★★ same type
DOCK8 c.529-2A>G Likely pathogenic ★★ same type
DOCK8 p.Arg1388Ter Pathogenic ★★ same type
DOCK8 p.Arg1796Ter Pathogenic ★★ same type

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-met2022val (accessed [today's date]).

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