Is DOCK2 p.Val984Met (c.2950G>A) pathogenic?

DOCK2 p.Val984Met (c.2950G>A) is classified Uncertain significance in DOCK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-04). AlphaMissense: likely pathogenic (0.8315); Very rare (popmax 0.00835%, amr); Associated with Inborn genetic diseases.

What condition is associated with DOCK2 p.Val984Met (c.2950G>A)?

DOCK2 p.Val984Met (c.2950G>A) is associated with Inborn genetic diseases, DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Val984Met (c.2950G>A) in the general population?

DOCK2 p.Val984Met (c.2950G>A) is very rare (popmax 0.00835%, amr) (gnomAD).

What do computational predictors say about DOCK2 p.Val984Met (c.2950G>A)?

AlphaMissense predicts likely pathogenic (score 0.8315) — an in-silico prediction, not a clinical call.

DOCK2 p.Val984Met

c.2950G>A · rs768478391 · VCV1517859

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8315 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00835%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8315	likely pathogenic
REVEL	0.257	benign-leaning
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 348 kb · p 3.1e-21 · regional, not allelic
Overall
CADD	29.9	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 0.00835% Admixed American · 5/59,846 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00161% 26/1,610,682 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00835%	11,969
East Asian	0.00446%	22,404
African / African-American	0.00267%	37,415
European (non-Finnish)	0.00144%	69,297

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: DOCK2
Protein: p.Val984Met
Coding: c.2950G>A
MANE Select: NM_004946
dbSNP: rs768478391
Type: single nucleotide variant
Location: chr5:169985879 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 984: the 'interaction with crkl' region

Full DOCK2 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: DOCK2 deficiency

Similar variants

DOCK2 c.2267+3G>A Uncertain significance ★★ same condition
DOCK2 c.2704-3C>T Uncertain significance ★★ same condition
DOCK2 c.4467+4A>G Uncertain significance ★★ same condition
DOCK2 p.Ala1393Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1710Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1765Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala24Pro Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala454Val Uncertain significance ★★ ⚠ 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/dock2-p-val984met (accessed [today's date]).

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