Is DOCK2 p.Ala1765Glu (c.5294C>A) pathogenic?

DOCK2 p.Ala1765Glu (c.5294C>A) is classified Uncertain significance in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: likely benign (0.2736); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with DOCK2 p.Ala1765Glu (c.5294C>A)?

DOCK2 p.Ala1765Glu (c.5294C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK2 p.Ala1765Glu (c.5294C>A) in the general population?

DOCK2 p.Ala1765Glu (c.5294C>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about DOCK2 p.Ala1765Glu (c.5294C>A)?

AlphaMissense predicts likely benign (score 0.2736) — an in-silico prediction, not a clinical call.

DOCK2 p.Ala1765Glu

c.5294C>A · rs141274816 · VCV2245497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2736	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -6.83	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 2.6	GERP 0.45, phastCons 0.76
Regional constraint	o/e 0.88	unconstrained · MANE · 33 kb · p 0.0025 · regional, not allelic
Overall
CADD	17.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/90,882 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000274% 4/1,460,454 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,441
European (non-Finnish)	0.00017%	589,710

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.Ala1765Glu
Coding: c.5294C>A
MANE Select: NM_004946
dbSNP: rs141274816
Type: single nucleotide variant
Location: chr5:170081848 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB

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.Ala1765Val Uncertain significance ★★ ⚠ same residue
DOCK2 p.Ala1765= Benign/Likely benign ★★ same residue
DOCK2 p.Ala1765Gly Uncertain significance ★ ⚠ same residue
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.Arg1274Gln 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-ala1765glu (accessed [today's date]).

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