Is DOCK2 p.Ser1688Arg (c.5062A>C) pathogenic?

DOCK2 p.Ser1688Arg (c.5062A>C) is classified Uncertain significance in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.1857); Ultra-rare (popmax 0.0174%, afr); Associated with Inborn genetic diseases.

What condition is associated with DOCK2 p.Ser1688Arg (c.5062A>C)?

DOCK2 p.Ser1688Arg (c.5062A>C) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK2 p.Ser1688Arg (c.5062A>C) in the general population?

DOCK2 p.Ser1688Arg (c.5062A>C) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about DOCK2 p.Ser1688Arg (c.5062A>C)?

AlphaMissense predicts likely benign (score 0.1857) — an in-silico prediction, not a clinical call.

DOCK2 p.Ser1688Arg

c.5062A>C · VCV4014096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1857 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1857	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -7.90	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 8.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 33 kb · p 0.0025 · regional, not allelic
Overall
CADD	21.3	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 0.0174% African / African-American · 13/74,880 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00155% 25/1,613,940 alleles · ultra-rare exomes 17/1,461,856 · genomes 8/152,084 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,760
Admixed American	0.01%	9,999
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.000339%	295,003

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.Ser1688Arg
Coding: c.5062A>C
MANE Select: NM_004946
Type: single nucleotide variant
Location: chr5:170079042 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 1688: the 'disordered' 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

Similar variants

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.Arg1274Gln 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-ser1688arg (accessed [today's date]).

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