Is DOCK2 p.Arg1274Trp (c.3820C>T) pathogenic?

DOCK2 p.Arg1274Trp (c.3820C>T) is classified Uncertain significance in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-22). AlphaMissense: likely pathogenic (0.5712); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with DOCK2 p.Arg1274Trp (c.3820C>T)?

DOCK2 p.Arg1274Trp (c.3820C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK2 p.Arg1274Trp (c.3820C>T) in the general population?

DOCK2 p.Arg1274Trp (c.3820C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DOCK2 p.Arg1274Trp (c.3820C>T)?

AlphaMissense predicts likely pathogenic (score 0.5712) — an in-silico prediction, not a clinical call.

DOCK2 p.Arg1274Trp

c.3820C>T · VCV3841926

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5712 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5712	likely pathogenic
REVEL	0.213	benign-leaning
SaProt	LLR -13.94	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -1.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 348 kb · p 3.1e-21 · regional, not allelic
Overall
CADD	27.9	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00149% 24/1,613,412 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
African / African-American	0.00668%	14,973
East Asian	0.00223%	44,844
Remaining individualsnot grpmax-eligible	0.0016%	62,438
European (non-Finnish)	0.00136%	73,732

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.Arg1274Trp
Coding: c.3820C>T
MANE Select: NM_004946
Type: single nucleotide variant
Location: chr5:170042076 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 1274: the docker domain; the 'interaction with crkl' region; an α-helix

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

Similar variants

DOCK2 p.Arg1274Gln Uncertain significance ★★ ⚠ same residue
DOCK2 p.Ala1765Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala812Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Arg1071Cys Uncertain significance ★★ ⚠ same condition
DOCK2 p.Arg11Gln Uncertain significance ★★ ⚠ same condition
DOCK2 p.Arg1200His Uncertain significance ★★ ⚠ same condition
DOCK2 p.Arg1480Cys Uncertain significance ★★ ⚠ same condition
DOCK2 p.Arg1480His 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-arg1274trp (accessed [today's date]).

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