Is DOCK2 p.Phe19Leu (c.57C>G) pathogenic?

DOCK2 p.Phe19Leu (c.57C>G) is classified Uncertain significance in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely pathogenic (0.9862); Absent from gnomAD v4.1; Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.Phe19Leu (c.57C>G)?

DOCK2 p.Phe19Leu (c.57C>G) is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Phe19Leu (c.57C>G) in the general population?

DOCK2 p.Phe19Leu (c.57C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK2 p.Phe19Leu (c.57C>G)?

AlphaMissense predicts likely pathogenic (score 0.9862) — an in-silico prediction, not a clinical call.

DOCK2 p.Phe19Leu

Q: How is Combined immunodeficiency due to DOCK2 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.57C>G · rs2532379042 · VCV2000716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9862 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DOCK2 deficiency

Computational evidence

Protein change
AlphaMissense	0.9862	likely pathogenic · top 9% in DOCK2
REVEL	0.285	benign-leaning
SaProt	LLR -10.63	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 1.4	GERP -0.17, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 63 kb · p 1.8e-09 · regional, not allelic
Overall
CADD	24.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOCK2
Protein: p.Phe19Leu
Coding: c.57C>G
MANE Select: NM_004946
dbSNP: rs2532379042
Type: single nucleotide variant
Location: chr5:169654416 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 19: the sh3 domain

Full DOCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DOCK2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to DOCK2 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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-phe19leu (accessed [today's date]).

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